Search

Background: The branched-chain amino acids (BCAAs) to tyrosine (Tyr) ratio (BTR) test is used to evaluate the progression of chronic liver disease (CLD). However, the differences across sex, age, body mass index (BMI) and etiologies are still unclear. Methods: We retrospectively reviewed data from 2,529 CLD cases with free amino acids (FAAs) in peripheral blood from four hospitals and 16,421 general adults with FAAs data from a biobank database. In total, 1,326 patients with CLD (covering seven etiologies) and 8,086 healthy controls (HCs) were analyzed after exclusion criteria. We investigated the change of BTR in HCs by sex, age and BMI and then compared these to patients divided by modified ALBI (mALBI) grade after propensity score matching. Results: BTR is significantly higher in males than females regardless of age or BMI and decreases with aging in HCs. In 20 types of FAAs, 7 FAAs including BCAAs were significantly decreased, and 11 FAAs including Tyr were significantly increased by mALBI grade in total CLD. The decreasing timings of BTR were at mALBI grade 2b in all CLD etiologies compared to HCs, however in chronic hepatitis C (CHC), chronic hepatitis B (CHB) and alcoholic liver disease (ALD), BTR started to decrease at 2a. There was a positive correlation between BCAAs and albumin among parameters in BTR and mALBI. The correlation coefficients in PBC, ALD and MASLD were higher than those of other etiologies. Conclusions: BTR varies by sex and age even among healthy adults, and decreasing process and timing of BTR during disease progression is different among CLD etiologies. [ABSTRACT FROM AUTHOR]

Background: HBV DNA assays have several limitations including being expensive and not widely available. Detection of HBsAg in serum has been the hallmark of HBV infection. However, previous studies regarding the association between HBsAg and HBV DNA revealed contradictory results. This study aims to reassess the correlation between HBsAg and HBV DNA in chronic hepatitis B patients. Methods: Observational studies with näive chronic hepatitis B patients were included, while studies with other coinfections were excluded. The studies were identified by searching through Google Scholar, PubMed, ScienceDirect, and Springer Link for English and Bahasa articles from 2011 to 2021. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) was followed. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal. Results: A total of 17 studies with 4134 participants met the criteria. The overall analysis revealed a moderate correlation between quantitative HBsAg and quantitative HBV DNA in the total sample of chronic hepatitis B patients (r = 0.57, 95% CI 0.40–0.75, P < 0.00001). In HBeAg + group, a moderate correlation was indicated while in HBeAg − revealed a weak association (r = 0.55, 95% CI 0.39–0.70, P < 0.00001 vs r = 0.29, 95% CI 0.20–0.38, P < 0.00001). The strongest correlation was discovered in HBeAg + chronic HBV infection phase (r = 0.59, 95% CI 0.35–0.82, P < 0.00001). Conclusion: Serum HBsAg titer supports as a predictor of serum HBV DNA levels in clinical practice with moderate strength of correlation. Trial registration: This review had been registered in PROSPERO (ID: CRD42023421246). [ABSTRACT FROM AUTHOR]

Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated. [ABSTRACT FROM AUTHOR]

Background: Cyproheptadine is an easily available over-the-counter first-generation antihistaminic that is often used as an appetite stimulant. Although it is usually a safe drug, rare instances of drug-induced liver injury may occur. Case presentation: We report a case of cholestatic liver injury secondary to cyproheptadine in a young pharmacy student with chronic hepatitis B and review the literature of cyproheptadine-induced liver injury. Conclusion: Although cyproheptadine is largely a safe drug, its potential for significant liver toxicity cannot be ignored. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis-B virus (HBV) infection due to mother-to-child transmission (MTCT) during the perinatal period is an important global health concern. Chile is a low-prevalence country with an increasing migratory inflow from Latin- American countries, with intermediate to high endemic rates of HBV infection, and until 2021, there is no universal maternal screening. This study aimed to evaluate infant outcomes using a risk-based strategy of maternal screening to prevent MTCT of hepatitis B virus (HBV) in a low-prevalence country. Methods: This prospective study included infants born to HBsAg-positive women detected using a local risk-based strategy. The exposed infants received immunoprophylaxis (IP) and follow-up to evaluate their clinical outcomes and immune responses through post-serological vaccine testing (PSVT) after completing the three- dose schedule of the HBV vaccine. Results: A total of 99 HBsAg-positive mothers were detected. Seventy-six (82%) infants completed the follow-up and had PSVT between 9 and 12 months of age. 55.2% female, the median gestational age was 39 weeks (25–41) and the median birth weight was 3,130g (816–4,400 g). All patients received IP with recombinant HBV vaccine plus hepatitis-B virus immunoglobulin (HBIG) and three doses of the HBV vaccine. There were no cases of HBV infection, and 96% (72) responded to immunization with HBsAg antibodies (anti-HBsAg) >10 UI/ml, with a median level of 799 IU/ml. Conclusions: A high-risk strategy can be implemented in countries with non-universal screening for VHB. Timely IP plus high-uptake VHB vaccination in infants born to HBsAg-positive mothers was associated with a high immunogenic response and absence of MTCT. Significance: What's it's already known on this subject?: There is robust evidence that immunoprophylaxis is recommended in all infants born to a HBsAg positive mother like one of different strategies to control VHBtransmission. What this study adds?: In countries with non-universal screening of VHB a risk based strategy could be considered to prevent MTCT. Timely immunoprophylaxis plus high uptake VHB vaccination in infants born to HBsAg positive mothers is associated with a high immunogenic response and no MTCT. PVST should be considered in populations with lower immunogenic response such as infants born with <2,000 g of weight. PVST should be performed 1 or 2 months after the priming vaccine doses, helping to avoid unnecessary revaccination due to expected declining seroprotecting levels through time. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of serum alpha-fetoprotein (AFP) in diagnosing subcentimeter hepatocellular carcinoma (HCC) on gadoxetic acid–enhanced MRI (EOB-MRI). Methods: This study retrospectively enrolled treatment-naïve patients with chronic hepatitis B who had a solitary subcentimeter observation on EOB-MRI from January 2017 to March 2023. Final diagnosis was confirmed by pathology for HCC and pathology or follow-up for benign controls. The AFP cutoff value for HCC was determined using Youden's index. Diagnostic criteria were developed according to significant findings in logistic regression analyses based on AFP and imaging features. The diagnostic performance of possible criteria was compared to the diagnostic hallmarks of HCC (arterial-phase hyperintensity and portal-phase hypointensity). Results: A total of 305 patients (mean age, 51.5 ± 10.7 years; 153 men) were divided into derivation and temporal validation cohorts. Four findings, namely AFP >13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity, were predictors of HCC. A new criterion (at least three of the four findings) showed higher sensitivity than the diagnostic hallmarks (derivation cohort, 71.6% vs. 52.3%, p < 0.001; validation cohort, 75.0% vs. 47.5%, p = 0.003) without decreasing specificity (derivation cohort, 92.5% vs. 92.5%, p > 0.999; validation cohort, 92.0% vs. 92.0%, p > 0.999). Another criterion (all four findings) achieved a slightly higher specificity than the diagnostic hallmark (derivation cohort, 99.1% vs. 92.5%, p = 0.023; validation cohort, 100.0% vs. 92.0%, p = 0.134). Subgroup analysis for hepatobiliary hypointense observations yielded similar results. Conclusion: Including AFP in the diagnostic algorithm may improve the diagnostic performance for subcentimeter HCC. Clinical relevance statement: Combining imaging features on gadoxetic acid–enhanced MRI with alpha-fetoprotein may enhance the diagnostic performance for subcentimeter HCC in treatment-naïve patients with chronic hepatitis B. Key Points: • The traditional diagnostic hallmark of HCC (arterial-phase hyperintensity and portal-phase hypointensity) shows modest diagnostic performance for subcentimeter HCC on EOB-MRI. • Serum alpha-fetoprotein > 13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity were independent predictors for subcentimeter HCC. • A criterion of at least three of the four above findings achieved a higher sensitivity without decreasing specificity. [ABSTRACT FROM AUTHOR]

Background & Aims: Concurrent hepatic steatosis has diverse effects on chronic hepatitis B (CHB), however the combined effects of metabolic dysfunction-associated steatotic liver disease (MASLD) and CHB on liver fibrosis progression remains unclear. The primary aim of this study was to utilize serial fibrosis measurements to compare the dynamic change in fibrosis in CHB patients with/without concurrent MASLD. The secondary aim was to investigate factors associated with steatosis development and regression in CHB patients. Methods: This was a retrospective cohort study of all non-cirrhotic CHB patients identified from 1/1/2011 to 31/12/2016. Hepatic steatosis was diagnosed by ultrasound. Fibrosis markers included liver stiffness (LSM) by transient elastography, APRI and FIB-4. General linear mixed effects modelling was used to fit polynomial and linear estimates. Results: Of 810 CHB patients (n = 2,373 LSM measurements; median age 44.4y; 48% male; 24% HBeAg positive), 14% had concurrent MASLD. LSM was higher at baseline but decreased in MASLD patients over time, while LSM remained stable in non-MASLD patients, such that all patients had similar LSM beyond 4–5 years. MASLD patients had lower APRI compared to non-MASLD patients, which was predominately due to a higher platelet count and higher ALT over time. There was substantial discordance between LSM, APRI and FIB-4. Baseline BMI was the only factor that predicted steatosis development and regression. Conclusions: We found no evidence of an association between concurrent MASLD and fibrosis progression amongst CHB patients without baseline advanced liver disease. APRI and FIB-4 may have reduced accuracy in MASLD patients. [ABSTRACT FROM AUTHOR]

Background: Currently, standard treatments for chronic hepatitis B such as nucleos(t)ide analogs (NAs), effectively reduce hepatitis B virus (HBV) loads but rarely result in a functional cure (defined as sustained HBsAg loss). We report the discovery of a novel, 4-pyridone compound, SAG-524, a potent and orally bioavailable small molecule inhibitor of HBV replication. Methods: The antiviral characteristics and selectivity of SAG-524 and its derivative compound against HBV were evaluated in HBV-infection assays and HBV-infected chimeric urokinase-type plasminogen activator/severe combined immunodeficiency mice with humanized livers (PXB mice), alone or in combination with entecavir. Toxicity studies were conducted in mice and monkeys. Results: SAG-524 reduced HBV-DNA (IC50 = 0.92 nM) and HBsAg (IC50 = 1.4 nM) in the supernatant of the HepG2.2.15 cells. SAG-524 selectively destabilized HBV-RNA via PAPD5, but not GAPDH or albumin mRNA, by shortening the poly(A) tail. PAPD5 may also be involved in HBV regulation via ELAVL1. In a study of HBV-infected PXB mice, SAG-524 produced potent reductions of serum HBsAg and HBcrAg, and the minimum effective dose was estimated to be 6 mg/kg/day. The combination therapy with entecavir greatly reduced HBsAg and cccDNA in the liver due to reduction of human hepatocytes with good tolerability. Administration of SAG-524 to monkeys, up to 1000 mg/kg/day for two weeks, led to no significant toxicity, as determined by blood tests and pathological images. Conclusions: We have identified SAG-524 as novel and orally bioavailable HBV-RNA destabilizers which can reduce HBsAg and HBV-DNA levels, and possibly contribute a functional cure. [ABSTRACT FROM AUTHOR]

Purpose: To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine. Methods: An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600 mg once daily. Plasma concentration was measured 12 h after taking telbivudine using ultra-performance liquid chromatography–tandem mass spectrometry and SNPs located in RRM2B, TK2, and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant. Results: A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07–1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61 ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers. Conclusion: Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase. [ABSTRACT FROM AUTHOR]

Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve as an activated HSCs regulator via regulating NF2 and Hippo pathway. LncRNA SNHG5 can regulate the Hippo pathway and EMT process by interacting with NF2 to mediate the activation of hepatic stellate cells. [ABSTRACT FROM AUTHOR]

Chronic infection with Hepatitis B virus (HBV) significantly increases the risk of hepatocellular carcinoma (HCC), particularly in Eastern Asia. However, only a subset of individuals with chronic HBV infection develop HCC, suggesting the role for genetic factors in HCC etiology. Despite genome-wide association studies (GWASs) identifying multiple single nucleotide polymorphisms (SNPs) associated with HBV-related HCC susceptibility, the underlying mechanisms and causal genetic polymorphisms remain largely unclear. To address this, we developed The Updated Integrative Functional Genomics Approach (TUIFGA), an methodology that combines data from transcription factor (TF) cistromics, ATAC-seq, DNAase-seq, and the 1000 Genomes Project to identify cancer susceptibility SNPs within TF-binding sites across human genome. Using TUIFGA, we discovered SNP rs13170300 which located in the TF MAZ binding motif of RPS14. The RPS14 rs13170300 was significantly associated with HCC risk in two case–control sets, with the T allele as the protective allele (Shandong discovery set: TT OR = 0.60, 95% CI = 0.49–0.74, P = 1.0 × 10–6; CT OR = 0.69, 95% CI = 0.55–0.86, P = 0.001; Jiangsu validation set: TT OR = 0.70, 95% CI = 0.56–0.87, P = 0.001; CT OR = 0.65, 95% CI = 0.53–0.82, P = 1.6 × 10–4). SNP rs13170300 affected MAZ binding in the RPS14 promoter, resulting in allele-specific changes in gene expression. RPS14 functions as a novel oncogene in HCC, specifically via activating the AKT signaling. Our findings present important insights into the functional genetics underlying HBV-related HCC development and may contribute to personalized approaches for cancer prevention and novel therapeutics. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. Objective: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. Methods: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. Results: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = − 17.27, 95% CI (− 30.03, − 4.47); TDF vs. non-HBV-infected individuals: MD = − 17.10, 95% CI (− 20.13, − 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = − 2.69, 95% CI (− 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = − 2.52, 95% CI (− 8.47, 3.43); ETV vs. inactive CHB patients: MD = − 4.24, 95% CI (− 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = − 4.07, 95% CI (− 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). Conclusion: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection poses a significant global health challenge, impacting millions of individuals and elevating the risk of morbidity and mortality. Antiviral therapies are the primary treatment for chronic HBV infection, but treatment resistance can occur, leading to poor clinical outcomes and an increased risk of liver complications. This case report presents the clinical trajectory of a 28-year-old male diagnosed with asymptomatic HBV infection in 2016 under the auspices of the Hepatitis Control Program, Government of Azad Jammu and Kashmir, Pakistan. Over 6 years, persistent HBsAg, HBV, and HBeAg were observed, with absent acute markers and co-infections. Initial HBV DNA viral load was 1 × 104 copies/mL in 2016, escalating despite entecavir and pegylated interferons therapy, indicating multi-drug resistance. Tenofovir therapy initially reduced viral load but later exacerbated it, reaching 1.86 × 106 copies/mL in 2022. Liver function abnormalities and lipid profile irregularities persisted. Urine examination consistently showed abnormalities. Pending HBV DNA sequencing results may offer insights into treatment resistance. This case underscores the need for an adaptive approach in managing chronic HBV infections within public health programs. Continuous monitoring, integration of virological and biochemical data, and a tailored treatment strategy are essential for optimizing outcomes in similar cases, stressing the importance of refining therapeutic approaches against chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. Methods: Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. Results: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4–chr10, chr13–chr21, chr15–chr22, and chr16–chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A–B or B–A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000–6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients. Conclusion: This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development. [ABSTRACT FROM AUTHOR]

Background: We determined the long-term clinical outcome and the durability of treatment cessation after HBsAg seroclearance following nucleos(t)ide analog (NA) therapy in patients with chronic hepatitis B (CHB). Methods: We analyzed virological relapse (VR), HBsAg reversion, clinical relapse, and changes in HBsAg and HBcrAg levels by iTACT assay after treatment cessation of 90 CHB patients who achieved HBsAg seroclearance by NA treatment. Results: Median age of patients at treatment cessation was 57 years. Median duration of NA treatment and follow-up from cessation of NA were 9.25 and 5.2 years, respectively. Although VR occurred in 19 of 90 (21.1%) patients, HBV DNA levels of 18 patients had temporal elevations and sustained levels under the detection level thereafter. HBsAg reversion using Architect HBsAg QT assay occurred in six patients (6.7%) after cessation of NA. Five patients had temporal HBsAg level elevations and sustained levels under the detection level thereafter. One patient had virological and clinical relapse at 6 months after cessation of NA, and received NA re-treatment. HBsAg levels by iTACT assay from end of treatment (EOT) gradually decreased and in 18 of 28 (64%) patients reached an undetectable level at 5 years after EOT. In contrast, HBcrAg levels by iTACT assay slowly decreased, and in 8 of 29 patients (28%) reached an undetectable level at 5 years after EOT. Conclusions: Patients receiving NA treatment who achieved HBsAg seroclearance as determined by HBsAg QT assay rarely experienced virological or clinical relapse after the cessation of treatment. [ABSTRACT FROM AUTHOR]

Studies from high endemic areas, mostly China, indicate that surface antigen positive (HBsAgpos) chronic hepatitis B virus (HBV) infection is associated with an increased risk of developing diffuse large B-cell lymphoma (DLBCL), whereas studies in low endemic areas have provided conflicting results. Past infection, serologically defined by negative HBsAg and positive anti-core antibody (HBsAgnegHBcAbpos), has also been suggested to increase the risk of B-cell non-Hodgkin's lymphoma (NHL) in high endemic areas. We retrospectively reviewed unselected clinical records of 253 patients with DLBCL (54% male, aged 60.3 ± 14.6 years at diagnosis) and 694 patients with different types of indolent B-cell NHL (46% male, aged 61.7 ± 12.8 years). Patients were seen at a single center in Italy between 2001 and 2022 and HBV serological status (HBsAg, HBsAb, HBcAb, HBeAg, HBeAb, and HBV DNA) was analyzed through enzyme-linked immunosorbent assays and molecular assays; patients infected with hepatitis C virus or human immunodeficiency virus were excluded. We used an unconditional multiple logistic regression model including as matching variables gender, age at diagnosis, immigrant status, and HBV serological status. Patients with DLBCL had, compared to indolent NHL, a higher prevalence of HBsAgpos active infection (odds ratio (OR) 2.8, 95% confidence interval (95% CI) 1.2–6.3, p = 0.014). Strikingly, patients with DLBCL had also a significantly higher prevalence of past infection (OR 2.4, 95% CI 1.5–4.0, p = 0.0006). Male gender was associated with increased risk of DLBCL independently of the HBV serological status. These findings suggest that both past and active HBV infection may increase the risk of DLBCL in a low endemic area. Our study needs confirmation by studies in areas or populations with different rates of chronic or past HBV infection. [ABSTRACT FROM AUTHOR]

Background: The accurate evaluation of liver fibrosis is crucial for the treatment and follow up of chronic hepatitis B (CHB) patients. Aim: We examined the efficiency of serum Mac-2 Binding Protein Glycosylation isomer (M2BPGi) in diagnosing liver fibrosis stages in CHB patients. Methods: A cross-sectional study was conducted on 177 adult CHB patients visiting the University Medical Center Ho Chi Minh City, Vietnam between October 2019 and December 2021. M2BPGi, ARFI, APRI, and FIB-4 were tested against FibroScan® for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The optimal M2BPGi cut-off values were identified based on the area under the receiver operating characteristic (AUROC) curve. Results: There was a strong agreement between M2BPGi and FibroScan® (r = 0.77, P < 0.001). The optimal M2BPGi cut-off index (C.O.I) for detecting significant fibrosis (F ≥ 2) was 0.79 with an AUROC of 0.77, 67.3% sensitivity, 70% specificity, 60.6% NPV, and 75.3% PPV. Compared with APRI (61%) and FIB-4 (47%), M2BPGi had the greatest sensitivity for diagnosing F ≥ 2. M2BPGi combined with APRI yielded highest diagnosis performance for F ≥ 2 with an AUROC of 0.87. The optimal cut-off index of M2BPGi for diagnosing cirrhosis (F4) was 1.3 with an AUROC of 0.91, 88% sensitivity, 87.4% specificity, 97% NPV, and 61% PPV. The AUROC of M2BPGi for diagnosing F4 was comparable to that of ARFI (0.93). Conclusions: With cut-off values of 0.79 C.O.I and 1.3 C.O.I, M2BPGi could be an effective method for diagnosing significant fibrosis and cirrhosis in CHB patients, respectively. [ABSTRACT FROM AUTHOR]

Background and Aims: We and others have previously described that hepatitis B surface antibody (anti-HBs) seems to protect against clinically significant HBV reactivation in cohort studies of patients undergoing anti-tumor necrosis factor (TNF) therapy. However, there were too few cases of HBV reactivation within cohort studies to assess the role of anti-HBs titer on reactivation. The purpose of this study was to systematically review the correlation between anti-HBs titer and the degree of clinically relevant HBV reactivation in patients undergoing anti-TNF therapy. Methods and Results: We systemically reviewed all studies discussing anti-TNF therapy in patients with resolved HBV infection, defined as hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive. We identified a total of 48 cases of reactivation from 5 cohort studies and 10 case reports or case series; 21 were anti-HBs negative, 7 were only reported as anti-HBs positive, 16 were anti-HBs positive with titer below 100, and 4 were anti-HBs positive with titer above 100. HBsAg sero-reversion was dominantly seen in patients with negative, low and/or declining anti-HBs titers. There was a significant trend toward less clinically relevant form of reactivation with increase in baseline anti-HBs titer (p = 0.022). Conclusion: Anti-HBs titers greater than 100 iU/L protect against clinically relevant HBV reactivation, while patients with low anti-HBs titers or negative anti-HBs had more clinically relevant HBV reactivation and higher rates of HBsAg sero-reversion. This suggests the importance of baseline quantitative anti-HBs prior to starting anti-TNF therapy and consideration vaccination for boosting anti-HBs titers prior to and/or during therapy. [ABSTRACT FROM AUTHOR]

Aims: Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers. Methods: Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs. TDF alone) for 192 weeks. Participants completed a Symptom Checklist at baseline and every 4–12 weeks. A total symptom score was created, ranging from 0 (none) to 40 (severe). The SF-36 was completed every 48 weeks. Associations of symptom scores with ALT and viral markers were evaluated at baseline and end of treatment. Results: Participants were 65% male, 83% Asian, with a mean age of 42. Baseline symptoms were mild (median = 2, range 0–25) and associated with baseline ALT, HBV DNA levels and HBeAg + status. Patients on TDF alone experienced a more rapid and greater improvement in symptoms, but by week 192, symptom improvement was similar in both groups (54% vs 36%). Symptom improvements correlated with ALT and HBV DNA, most markedly among those with symptoms at baseline. Most patients (4 out of 6) who achieved HBsAg loss experienced symptom improvements. Overall, SF-36 scores did not change with treatment. Conclusions: Reduction in ALT and HBV DNA levels with therapy are associated with significant improvement in liver symptoms such as fatigue and pain over the liver, especially among those with higher ALT, HBV DNA, symptoms and HBeAg + status prior to treatment. [ABSTRACT FROM AUTHOR]

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA. [ABSTRACT FROM AUTHOR]

Background: Chemokines play a vital role in tumor progression, metastasis and prognosis; however, the profile and clinical significance of gamma interferon-inducible protein-10 (IP-10) and its receptor (CXCR3) in patients with hepatocellular carcinoma (HCC) have not been well evaluated. Methods: Liquid-phase chip technology was used to detect the serum IP-10 in 85 patients with HBV-related HCC, 50 patients with chronic hepatitis B (CHB) and 50 liver cirrhosis subjects (CS); simultaneously, the CXCR3 and Alpha fetoprotein (AFP) were determined. Additionally, their mRNA or protein expression levels in peripheral blood mononuclear cells (PBMC), liver tumor and paracancerous tissues were quantified using qRT-PCR or ELISA. Moreover, the IP-10 and CXCR3 expression was verified by the online data from Gene Expression Omnibus. Furthermore, the relationships of serum IP-10, CXCR3 and AFP levels with their overall survival rate were also analyzed. Results: The levels of IP-10 and CXCR3 in HCC group were significantly higher than those in CHB and CS groups, and their mRNA of PBMC is significantly positive correlation with those in their liver tissues or HBV DNA load (P < 0.0001), respectively. The serum IP-10 and CXCR3 in HCC were significantly correlated with tumor differentiation, metastases staging and distant metastasis (P < 0.05), but not related to gender, age and tumor size (P > 0.05, except IP-10 based on age). Conclusions: The serum IP-10 (142.6 pg/mL) and CXCR3 (241.2 pg/mL) could be differential diagnostic surrogates that distinguish HCC from CS, and the lower IP-10 level may be conducive to the postoperative survival of HCC patients. Moreover, the IP-10 and CXCR3 would be related to anti-tumor immunity in HCC patients and be a potential target for treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: Recently, the conversion therapies of FOLFOX-HAIC for patients with unresectable hepatocellular carcinoma (uHCC) have dramatically increased the tumor responses and conversion rate; thus, the prognosis of uHCC patients was expected to be prolonged. However, the postoperative recurrence of uHCC patients who successfully underwent conversion therapies stayed high. The present study evaluated the efficacy and safety of postoperatively adjuvant therapy in treating uHCC patients who received FOLFOX-HAIC-based conversion therapy. Methods: In this real-world retrospective study, uHCC patients who received FOLFOX-HAIC-based conversion therapy were included. The recurrence-free survival (RFS), as primary outcomes, was compared between patients who received adjuvant therapy (AT group) or non-adjuvant therapy (nAT group) using survival analysis and Cox regression. Imbalances in baseline clinical features between the two groups were adjusted through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Results: Between January 2016 and December 2022, 204 uHCC patients who received FOLFOX-HAIC-based conversion therapy were included and assigned into AT group (n = 47) and nAT group (n = 157), respectively. The median RFS was significantly longer in the AT group than the nAT group before adjustment [19.2 vs. 10.8 months; hazard ratio (HR), 0.584; 95% CI, 0.383–0.892; P = 0.028], after PSM and after IPTW. Subsequent subgroup analyses revealed the RFS of adjuvant therapy was best in uHCC patients with younger than 60 years, macrovascular invasion, and positive hepatitis B surface antigen. Conclusion: Postoperatively, adjuvant therapy was associated with improved survival outcomes compared with non-adjuvant therapy after FOLFOX-HAIC-based conversion therapy among uHCC patients, especially for patients with macrovascular invasion and positive hepatitis B surface antigen. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively inhibit virus replication; however, these treatments cannot cure HBV and novel treatment-strategies should be necessary. In this study, we identified tripartite motif-containing protein 26 (TRIM26) could be a supportive factor for HBV replication. Small interfering RNA-mediated TRIM26 knockdown (KD) modestly attenuated HBV replication in human hepatocytes. Endogenous TRIM26 physically interacted with HBV core protein (HBc), but not polymerase and HBx, through the TRIM26 SPRY domain. Unexpectedly, TRIM26 inhibited HBc ubiquitination even though TRIM26 is an E3 ligase. HBc was degraded by TRIM26 KD in Huh-7 cells, whereas the reduction was restored by a proteasome inhibitor. RING domain-deleted TRIM26 mutant (TRIM26ΔR), a dominant negative form of TRIM26, sequestered TRIM26 from HBc, resulting in promoting HBc degradation. Taking together, this study demonstrated that HBV utilizes TRIM26 to avoid the proteasome-dependent HBc degradation. The interaction between TRIM26 and HBc might be a novel therapeutic target against HBV infection. [ABSTRACT FROM AUTHOR]

Patients with chronic liver disease progressed to compensated advanced chronic liver disease (cACLD), the risk of liver-related decompensation increased significantly. This study aimed to develop prediction model based on individual bile acid (BA) profiles to identify cACLD. This study prospectively recruited 159 patients with hepatitis B virus (HBV) infection and 60 healthy volunteers undergoing liver stiffness measurement (LSM). With the value of LSM, patients were categorized as three groups: F1 [LSM ≤ 7.0 kilopascals (kPa)], F2 (7.1 < LSM ≤ 8.0 kPa), and cACLD group (LSM ≥ 8.1 kPa). Random forest (RF) and support vector machine (SVM) were applied to develop two classification models to distinguish patients with different degrees of fibrosis. The content of individual BA in the serum increased significantly with the degree of fibrosis, especially glycine-conjugated BA and taurine-conjugated BA. The Marco-Precise, Marco-Recall, and Marco-F1 score of the optimized RF model were all 0.82. For the optimized SVM model, corresponding score were 0.86, 0.84, and 0.85, respectively. RF and SVM models were applied to identify individual BA features that successfully distinguish patients with cACLD caused by HBV. This study provides a new tool for identifying cACLD that can enable clinicians to better manage patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

This article examines hepatitis B dynamics under distinct infection phases and multiple transmissions. We formulate the epidemic problem based on the characteristics of the disease. It is shown that the epidemiological model is mathematically and biologically meaningful of its well-posedness (positivity, boundedness, and biologically feasible region). The reproductive number is then calculated to find the equilibria and the stability analysis of the epidemic model is performed. A backward bifurcation is also investigated in the proposed epidemic problem. With the help of two control measures (treatment and vaccination), we develop control strategies to minimize the infected population (acute and chronic). To solve the proposed control problem, we utilize Pontryagin's Maximum Principle. Some simulations are conducted to illustrate the investigation of the analytical work and the effect of control analysis. [ABSTRACT FROM AUTHOR]

Purpose: Chronic hepatitis B-liver cirrhosis-hepatocellular carcinoma (CLH), commonly called the "liver cancer trilogy", is a crucial evolutionary phase in the emergence of hepatocellular carcinoma (HCC) in China. Previous studies on early diagnostic biomarkers of HCC were limited to the end-stage of HCC and did not focus on the evolutionary process of CLH. Methods: 11 monotonically changing differentially expressed genes (MCDEGs) highly correlated with CLH were screened through bioinformatic analysis and KPNA2 was identified for further research. The serum KPNA2 expression in different CLH states was detected by Enzyme linked immunosorbent assay (ELISA). A nomogram model was constructed using univariate and multivariate Cox regression methods. Results: The single-cell RNA-seq and bulk RNA-seq revealed that KPNA2 related to immune infiltration in HCC and may participate in cell cycle pathways in HCC. The serum KPNA2 expression was monotonically upregulated in CLH and was valuable for diagnosing different CLH states. Besides, chronic hepatitis B(CHB) patients, liver cirrhosis (LC) patients, and HCC patients were classified into subgroups with distinct serum KPNA2 expressions. Accordingly, patients with different serum KPNA2 expressions displayed various clinicopathological features. The AUC value of the nomogram model was 0.959 in predicting the likelihood of developing HCC in CHB patients or LC patients. Finally, we found that KPNA2 expression was negatively correlated with the IC50 of four chemotherapeutic drugs in HCC. Conclusion: KPNA2 was a novel serum biomarker for diagnosing different CLH states, monitoring the dynamic evolution of CLH, and a new therapeutic target for intervening in the progression of CLH. [ABSTRACT FROM AUTHOR]

Purpose: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma during antiviral therapy. We aimed to clarify the values of alpha-fetoprotein (AFP), lectin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) for early warning of HCC. Methods: A total of 1348 CHB patients received antiviral therapy and follow-up every 26 weeks. Eighty-four patients with HCC were age-, sex-, and cirrhosis-matched with 168 controls. AFP, AFP-L3, and DCP were compared between the groups from 104 weeks before HCC diagnosis (− 104 w) to the time of diagnosis (0 w). Results: Of the 84 HCC patients, 60 (71.4%) had early-stage HCC, AFP increased from − 26 w, and AFP-L3 and DCP increased from − 78 w. However, levels were unchanged in controls. ΔAFP, ΔAFP-L3, and ΔDCP showed similar abilities for predicting HCC (P > 0.05). Receiver operating characteristic curve analysis showed that AFP had better diagnostic performance for HCC than AFP-L3, DCP, or their combination. The cut-off values of AFP, AFP-L3, and DCP were 5.3 ng/mL, 1.05%, and 31.5 mAU/mL, respectively. Notably, lower AFP values were required to diagnose HCC in patients with detectable HBV DNA (4.1 ng/mL) or elevated alanine aminotransferase (5.2 ng/mL). Conclusions: Changes in AFP, AFP-L3, and DCP can help to predict HCC in CHB patients receiving antiviral therapy. A lower AFP value is needed to diagnose HCC, especially in patients with detectable HBV DNA or elevated alanine aminotransferase. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hepatitis B virus (HBV) infection is associated with significant global morbidity and mortality. Low treatment rates are observed in patients living with HBV; the reasons for this are unclear. This study sought to describe patients' demographic, clinical and biochemical characteristics across three continents and their associated treatment need. Methods: This retrospective cross-sectional post hoc analysis of real-world data used four large electronic databases from the United States, United Kingdom and China (specifically Hong Kong and Fuzhou). Patients were identified by first evidence of chronic HBV infection in a given year (their index date) and characterized. An algorithm was designed and applied, wherein patients were categorized as treated, untreated but indicated for treatment and untreated and not indicated for treatment based on treatment status and demographic, clinical, biochemical and virological characteristics (age; evidence of fibrosis/cirrhosis; alanine aminotransferase [ALT] levels, HCV/HIV coinfection and HBV virology markers). Results: In total, 12,614 US patients, 503 UK patients, 34,135 patients from Hong Kong and 21,614 from Fuzhou were included. Adults (99.4%) and males (59.0%) predominated. Overall, 34.5% of patients were treated at index (range 15.9–49.6%), with nucleos(t)ide analogue monotherapy most commonly prescribed. The proportion of untreated-but-indicated patients ranged from 12.9% in Hong Kong to 18.2% in the UK; almost two-thirds of these patients (range 61.3–66.7%) had evidence of fibrosis/cirrhosis. A quarter (25.3%) of untreated-but-indicated patients were aged ≥ 65 years. Conclusion: This large real-world dataset demonstrates that chronic hepatitis B infection remains a global health concern; despite the availability of effective suppressive therapy, a considerable proportion of predominantly adult patients apparently indicated for treatment are currently untreated, including many patients with fibrosis/cirrhosis. Causes of disparity in treatment status warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose: AFP appears to be negative in about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP-negative HCC (AFPN-HCC). Patients and methods: The training set included 294 AFPN-HCC patients, 159 healthy objects, 63 patients with chronic hepatitis B(CHB), and 64 patients with liver cirrhosis (LC). And the validation set enrolled 137 healthy controls objects, 47 CHB patients and 45 patients with LC. LASSO, univariate, and multivariable logistic regression analysis were performed to construct the model and then transformed into a visualized nomogram. The receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were further used for validation. Results: Four variables including age, PIVKA-II, platelet (PLT) counts, and prothrombin time (PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95% CI 0.892–0.938) in training set and 0.942(95% CI 0.921–0.963) in validation set. We also found that the model had high diagnostic value for small-size HCC (tumor size < 5 cm) (AUC = 0.886) and HBV surface antigen-positive AFPN-HCC (AUC = 0.883). Conclusions: Our model was effective for discrimination of AFPN-HCC from patients with benign liver diseases and healthy controls, and might be helpful for the diagnosis for AFPN-HCC. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a rare and complicated disease with a high mortality rate. Emergency liver transplantation is the only treatment method that can improve the ALF prognosis. However, its clinical application remains limited owing to the aggressive nature of liver transplantation, limited donors, and high postoperative mortality. The study investigated the effect of m6A on the immune microenvironment of hepatitis B virus-related ALF (HBV-ALF). In this study, the gene expression data of 47 normal people and 42 HBV-ALF patients were downloaded from the Gene Expression Omnibu (GEO) database. The known 23 m6A regulators which mediated RNA modification patterns were compared and analyzed in these two groups, and the gene diagnosis model of HBV-ALF patients was established based on the analysis results. In addition, we used unsupervised clustering to identify different m6A RNA methylation modification patterns in HBV-ALF based on m6A regulators, and evaluated the immune infiltration and biological differences in these subtypes. In addition, the relationship between m6A genes and immune cell activation in HBV-ACLF patients was explored by immune infiltration analysis. Nineteen m6A regulators mediated RNA methylation (m6A regulators for short) were differentially expressed in HBV-ALF and control groups. m6A regulators could well distinguish control samples from HBV-ALF samples, and m6A regulators might be used as a basis for diagnosing HBV-ALF patients. Immune cells such as activated CD8 T cells, activated B cells, and activated CD4 T cells might play important roles in HBV-ALF, and m6A regulators were closely associated with immune cell infiltration. ALKBH15, CBLL1, IGF2BP2, IGF2BP3, and ZC3H13 were significantly associated with immune cells. Considering 23 m6A regulators, HBV-ALF patients could be classified into two subtypes (cluster 1 and cluster 2) based on different immune cell infiltration. m6A regulators of the IGFBP and YHDF families have extremely different levels in these two subtypes. Differential immune cell infiltration among these subtypes was observed, a total of 913 differentially expressed genes among different m6A modification patterns was identified, and their biological functions were explored. m6A modification might play a crucial role in the diverse and complex immune microenvironment of HBV-ALF patients. [ABSTRACT FROM AUTHOR]

Introduction: Long-term complications of chronic hepatitis B (CHB) viral infection, such as cirrhosis, hepatocellular carcinoma (HCC), and liver failure, cause a large disease burden. This study aimed to describe the epidemiology, clinical outcomes, and treatment patterns of CHB infection and co-infection with hepatitis D virus (HDV) in South Korea. Methods: The retrospective, observational study used existing data from the Health Insurance Review and Assessment Service (HIRA) database. Confirmed cases of (CHB) and HBV/HDV co-infection were identified between 2013 and 2019. Hepatitis C virus co-infections and acute HBV infections were excluded. Incident cases diagnosed between 2015 and 2018 with no prior disease history up to 2 years were included. Patient characteristics, clinical outcomes, economic burden, and healthcare-resource utilization were described. Results: The estimated 7-year prevalence of CHB and HBV/HDV co-infection were 0.9% and 0.0024%, respectively. The prevalence was higher among 45–54 years old (CHB: 1.6%, HBV/HDV: 0.0049%) and males (1.1%, 0.0035%). The 5-year cumulative incidences of compensated cirrhosis, decompensated cirrhosis, HCC, and liver transplantation were 13.3%, 7.1%, 8.4%, and 0.7%, respectively. Hyperlipidemia (40.6%), hypertension (23.5%), and peptic ulcer (23.7%) were the more prevalent comorbidities. Among CHB patients, 48.1% received ≥ 1 prescribed anti-HBV drug including interferon or nucleos(t)ide analogues and 64.4% had ≥ 1 hospitalization compared to 80.4% and 79.4% HBV/HDV patients. Estimated total healthcare costs for CHB and HBV/HDV were US$786 million and $62 million, respectively. Conclusions: These findings provide insights to the epidemiology, clinical burden, treatment patterns, and healthcare costs of CHB and HBV/HDV co-infection in South Korea. [ABSTRACT FROM AUTHOR]

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are equally recommended as first-line treatments for antiviral treatment-naïve (ART-naïve) chronic hepatitis B (CHB) patients by practice guidelines because of their similarly high antiviral efficacy and low resistance rate. However, whether one is superior to the other in terms of hepatocellular carcinoma (HCC) prevention is currently largely controversial. We aimed to identify and synthesize these existing studies regarding the HCC risk of these two highly potent antivirals in treatment-naïve CHB patients. PubMed, EMBASE, and Cochrane Library were searched for studies between January 1, 2012 and June 25, 2022. These studies used ETV monotherapy and/or TDF monotherapy to treat ART-naïve CHB patients and reported the incidence of HCC. The extracted data were analyzed using a DerSimonian–Laird random-effects models. The HCC incidence difference was expressed as hazard ratio (HR) and 95% confidence interval (95% CI). A total of 17 studies with 90,897 ART-naïve CHB patients (ETV = 60,980 vs TDF = 29,917) were included in this meta-analysis. Compared with ETV, TDF was associated with a significant lower cumulative incidence of HCC (HR 0.66; 95% CI 0.56–0.76). No significant heterogeneity or publication bias was found among the included studies (I2 = 48.1%, Begg's p = 0.363 and Egger's p = 0.748). TDF is associated with a lower risk of HCC compared with entecavir in ART-naïve CHB patients. The results suggest that TDF may be a better option for ART-naïve CHB patients with high HCC risks. [ABSTRACT FROM AUTHOR]

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotrophic viruses, they may affect pulmonary diseases. The purpose of this study was to assess whether chronic viral hepatitis (CVH) infection was associated with a rapid decline in lung function. Repeated measurements of lung function were obtained from a well-curated health check-up database. A case was defined as an individual positive for HBsAg or anti-HCV antibody. A control was randomly selected (from the same dataset) after 1:1 matching in terms of age, sex, height, the body mass index, and smoking status. Separate analyses of non-smokers and smokers were performed. A total of 701 cases were enrolled (586 with HBV and 115 with HCV). In cross-sectional analysis, both forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decreased significantly only in smokers (smoking cases vs. smoking controls) (adjusted p = 6.6 × 10−5 and adjusted p = 2.2 × 10−3, respectively). In longitudinal analysis, smoking cases showed significantly greater FEV1 and FVC decline rates than did smoking controls (adjusted p = 8.5 × 10−3 and adjusted p = 1.2 × 10−5, respectively). Such associations were particularly high in smoking cases at intermediate-to-high risk of hepatic fibrosis, as evaluated by the non-invasive Fibrosis-4 index. In summary, CVH was associated with both decreased lung function and accelerated lung function decline in smokers. A non-invasive measurement of hepatic fibrosis may be useful in predicting rapid lung function decline in smokers with CVH. [ABSTRACT FROM AUTHOR]

This letter discusses a case of recurrent abducens nerve palsy, which affects the motor control of the eye and causes double vision. The condition is typically caused by various factors, but the most common cause of recurring palsy is myasthenia gravis. However, in this particular case, the patient had a history of chronic hepatitis B infection, which was identified as the only identifiable risk factor. The patient was treated with corticosteroids and vitamins, and there was significant improvement in their symptoms. The letter emphasizes the importance of considering hepatitis viruses in the diagnostic workup of patients with recurrent cranial nerve palsies. [Extracted from the article]

Background: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. Methods: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. Results: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. Conclusions: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. Clinical relevance statement: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. Key points: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77. [ABSTRACT FROM AUTHOR]

The value of the different types of HDACs (histone deacetylases) for HCC (hepatocellular carcinoma) prognosis and clinicopathological features is still controversial. Here, we performed a meta-analysis to investigate the possible role of different types of HDACs in HCC. Until October 28, 2021, we have searched the Embase, Cochrane, PubMed, Scopus, Web of Science (WOS), SinoMed, Chinese China National Knowledge Infrastructure (CNKI), Chinese WanFang, and Chinese Weipu databases and evaluated eligible studies according to the criteria. We used hazard ratio (HR) and 95% confidence interval (95% CI) to evaluate the prognostic effects of different types of HDACs on overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and used odds ratio (OR) and corresponding 95% CI to evaluate the significance of HDACs on clinicopathological characteristics. The I2 statistic and chi-square-based Q test were used to assess the heterogeneity. When the heterogeneity was significant, we conducted a subgroup analysis. In addition, Egger's test and funnel chart were used to assess publication bias. The high expression of class I HDACs was associated with poorer OS, DFS/RFS and differentiation, intrahepatic metastasis, tumor-node-metastasis (TNM), tumor number, tumor size, vascular invasion, and other poor clinicopathological characteristics. The high expression of class II HDACs was related to poor OS and multiple and larger tumors. After subgroup analysis, class II HDACs may also be related to worse TNM and Edmondson grading. The high expression of class III HDACs was related to poor OS, hepatitis B, liver cirrhosis, serum AFP, and vascular invasion. But it was more common in women and was related to single, smaller tumors. Type I, II, and III HDACs are associated with poor prognosis, and there are also correlations with some clinicopathological features, suggesting that different types of HDACs may be valuable biomarkers for HCC. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively inhibit virus replication; however, these treatments cannot cure HBV and novel treatment-strategies should be necessary. In this study, we identified tripartite motif-containing protein 26 (TRIM26) could be a supportive factor for HBV replication. Small interfering RNA-mediated TRIM26 knockdown (KD) modestly attenuated HBV replication in human hepatocytes. Endogenous TRIM26 physically interacted with HBV core protein (HBc), but not polymerase and HBx, through the TRIM26 SPRY domain. Unexpectedly, TRIM26 inhibited HBc ubiquitination even though TRIM26 is an E3 ligase. HBc was degraded by TRIM26 KD in Huh-7 cells, whereas the reduction was restored by a proteasome inhibitor. RING domain-deleted TRIM26 mutant (TRIM26ΔR), a dominant negative form of TRIM26, sequestered TRIM26 from HBc, resulting in promoting HBc degradation. Taking together, this study demonstrated that HBV utilizes TRIM26 to avoid the proteasome-dependent HBc degradation. The interaction between TRIM26 and HBc might be a novel therapeutic target against HBV infection. [ABSTRACT FROM AUTHOR]

Patients with chronic liver disease progressed to compensated advanced chronic liver disease (cACLD), the risk of liver-related decompensation increased significantly. This study aimed to develop prediction model based on individual bile acid (BA) profiles to identify cACLD. This study prospectively recruited 159 patients with hepatitis B virus (HBV) infection and 60 healthy volunteers undergoing liver stiffness measurement (LSM). With the value of LSM, patients were categorized as three groups: F1 [LSM ≤ 7.0 kilopascals (kPa)], F2 (7.1 < LSM ≤ 8.0 kPa), and cACLD group (LSM ≥ 8.1 kPa). Random forest (RF) and support vector machine (SVM) were applied to develop two classification models to distinguish patients with different degrees of fibrosis. The content of individual BA in the serum increased significantly with the degree of fibrosis, especially glycine-conjugated BA and taurine-conjugated BA. The Marco-Precise, Marco-Recall, and Marco-F1 score of the optimized RF model were all 0.82. For the optimized SVM model, corresponding score were 0.86, 0.84, and 0.85, respectively. RF and SVM models were applied to identify individual BA features that successfully distinguish patients with cACLD caused by HBV. This study provides a new tool for identifying cACLD that can enable clinicians to better manage patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Objective: To develop and investigate a deep learning model with data integration of ultrasound contrast-enhanced micro-flow (CEMF) cines, B-mode images, and patients' clinical parameters to improve the diagnosis of significant liver fibrosis (≥ F2) in patients with chronic hepatitis B (CHB). Methods: Of 682 CHB patients who underwent ultrasound and histopathological examinations between October 2016 and May 2020, 218 subjects were included in this retrospective study. We devised a data integration-based deep learning (DIDL) model for assessing ≥ F2 in CHB patients. The model contained three convolutional neural network branches to automatically extract features from ultrasound CEMF cines, B-mode images, and clinical data. The extracted features were fused at the backend of the model for decision-making. The diagnostic performance was evaluated across fivefold cross-validation and compared against the other methods in terms of the area under the receiver operating characteristic curve (AUC), with histopathological results as the reference standard. Results: The mean AUC achieved by the DIDL model was 0.901 [95% CI, 0.857–0.939], which was significantly higher than those of the comparative methods, including the models trained by using only CEMF cines (0.850 [0.794–0.893]), B-mode images (0.813 [0.754–0.862]), or clinical data (0.757 [0.694–0.812]), as well as the conventional TIC method (0.752 [0.689–0.808]), APRI (0.792 [0.734–0.845]), FIB-4 (0.776 [0.714–0.829]), and visual assessments of two radiologists (0.812 [0.754–0.862], and 0.800 [0.739–0.849]), all ps < 0.01, DeLong test. Conclusion: The DIDL model with data integration of ultrasound CEMF cines, B-mode images, and clinical parameters showed promising performance in diagnosing significant liver fibrosis for CHB patients. Key Points: • The combined use of ultrasound contrast-enhanced micro-flow cines, B-mode images, and clinical data in a deep learning model has potential to improve the diagnosis of significant liver fibrosis. • The deep learning model with the fusion of features extracted from multimodality data outperformed the conventional methods including mono-modality data-based models, the time-intensity curve-based recognizer, fibrosis biomarkers, and visual assessments by experienced radiologists. • The interpretation of the feature attention maps in the deep learning model may help radiologists get better understanding of liver fibrosis-related features and hence potentially enhancing their diagnostic capacities. [ABSTRACT FROM AUTHOR]

Purpose: Cirrhosis is a diffuse pathology characterized by fibrosis of the liver and is the last stage of chronic liver diseases. It is a serious medical condition which seriously impacts reproduction and reproductive life span. The aim of this study is to evaluate the outcomes of pregnancies complicated with liver cirrhosis. Methods: Retrospective chart review of the fetal and maternal results of 20 pregnant women with liver cirrhosis who had undergone antenatal follow-up and delivery at a tertiary center in a 12-year period was performed. Results: Chronic hepatitis B was found to be the leading cause of liver cirrhosis in the study group, with a rate of 25% (n: 5/20). The average MELD score was calculated as 8.8 ± 3.5. Only three patients developed hepatic decompensation during pregnancy. Fetal demise was observed in 10% of the cases (n: 2/20, MELD scores 8 and 17). MELD score was significantly higher in the patients with adverse perinatal outcomes. Conclusion: Even though pregnancy is rarely observed in women with liver cirrhosis, many patients are able to achieve favorable maternal and fetal results without developing hepatic decompensation with appropriate management and close follow-up. The Model for End-Stage Liver Disease (MELD) score is a clinical tool utilized to estimate the severity and survival for chronic liver disease and was previously found to be associated with unfavorable outcomes in pregnant patients. Our study confirms this finding with the current experience from a tertiary care center. [ABSTRACT FROM AUTHOR]

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95%CI 0.01–0.09; I2 = 67.7%, P < 0.001). The pooled rates of HBV, HCV, and HIV reactivation were 0.04 (95%CI 0.00–0.10; I2 = 79.9%, P < 0.001), 0.07 (95%CI 0.02–0.14; I2 = 23.7%, P = 0.24), and 0.12 (95%CI 0.00–0.40), respectively. The pooled rates of HBV and HCV reactivation were 0.10 (95%CI 0.03–0.19) and 0.08 (95%CI 0.03–0.15) in Asia, but 0.00 (95%CI 0.00–0.01) and 0.04 (95%CI 0.00–0.21) in Europe. The publication type also influenced the results. The use of biological therapy in patients with psoriasis and HBV, HCV, or HIV infection might be associated with the rate of viral reactivation, but this meta-analysis had limitations, and the evidence might be weak. Nevertheless, it might suggest that at least a consultation with an infection specialist might be warranted in patients with psoriasis in whom biological therapies are considered. [ABSTRACT FROM AUTHOR]

Background: The prognostic effects of liver fibrosis and steatosis in patients with chronic hepatitis B or C are unclear. We investigated the prognostic effects of liver fibrosis and steatosis determined through transient elastography (TE) in patients with chronic hepatitis B or C. Methods: This retrospective cohort study enrolled 5528 patients with chronic hepatitis B or C who received TE. Multivariate Cox regression was used to evaluate the associations between fibrosis and steatosis grades and the occurrence of hepatic-related events, cardiovascular events, and mortality. Liver stiffness measurements of ≥ 7.1, ≥ 9.5, and ≥ 12.5 kPa were considered to indicate significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (≥ F4), and controlled attenuation parameters of ≥ 230 and ≥ 264 dB/m were considered to indicate mild (S1) and moderate-to-severe (S2–S3) steatosis, respectively. Results: During a median follow-up of 3.1 years, 489 patients died, 814 had hepatic-related events, and 209 had cardiovascular events. The incidences of these outcomes were lowest among individuals with no- or mild-fibrosis (F0–F1), and increased with fibrosis severity. The incidence of adverse outcomes was highest among patients without steatosis (S0) and lowest among those with moderate-to-severe steatosis. Adjusted models indicated that F2, F3, and F4 were independent risk factors and that moderate-to-severe steatosis was a favorable marker for hepatic-related events. Cirrhosis was an independent factor for mortality. Conclusions: According to TE, increasing fibrosis grades and absence of steatosis were associated with higher risks of hepatic-related events, whereas cirrhosis was a risk factor for mortality in patients with chronic hepatitis B or C. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC). Asian Americans have the highest incidence and mortality rates of HCC among all US racial/ethnic groups. Inadequate monitoring and treatment of chronic hepatitis B contribute to poor health outcomes and increased healthcare costs among Asian Americans. Aims: The goal of this study is to assess the effect of a patient-led strategy on chronic hepatitis B monitoring and treatment adherence specifically among Asian Americans with culturally tailored Patient Navigator-led Intervention. Methods: From 2015 to 2018, 532 eligible participants living with chronic hepatitis B in the greater Philadelphia and New York city metropolitan areas were randomly assigned to either the intervention group or the control group. Generalized linear mixed-effects models were used to estimate the odds ratio (OR) for rates of doctor visits for chronic hepatitis B and rates of alanine aminotransferase testing for evidence of liver damage. Results: Intervention group had higher rates of doctor visits than the control group at both 6-month (77.22% vs. 45.75%) and 12-month assessments (90.73% vs. 60.61%). Significantly more intervention group participants received ALT testing than control group participants at 6-month (52.90% vs. 25.10%) and 12-month (75.40% vs. 46.75%) follow-up. Conclusions: Culturally and linguistically appropriate intervention has strong effects on adherence to follow-up care among Asian American hepatitis B patients experiencing challenges to medication adherence and follow up care. These findings further identify opportunities for practical implementation of evidence-based intervention that could lead to reductions in disparities in chronic liver disease and liver cancer among high-risk, underserved populations. [ABSTRACT FROM AUTHOR]

Background and Aims: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). Methods: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. Results: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04–0.67, p = 0.01). Conclusion: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hepatitis B (CHB) is one of the world's major healthcare problems, especially in the Western Pacific regions. This study describes the prevalence, incidence, treatment profiles and clinical and economic burden of chronic hepatitis B patients in Japan using the Japan Medical Data Center (JMDC) Claims Database. Methods: This is a retrospective observational study. Prevalence cases were identified as patients with ≥ 1 inpatient or ≥ 2 outpatient CHB diagnoses and ≥ 2 records for hepatitis B tests or ≥ 1 prescription for CHB treatment between January 2010 and December 2019. Newly diagnosed CHB patients were defined as patients diagnosed from 2010 to 2018 with no history of the disease up to 2 years prior to the diagnosis. The index date is defined as the first CHB diagnosis day. We only used patients' data with ≥ 1-year post-index date. Results: We identified 13,061 CHB prevalent cases (2010–2019), yielding a crude period prevalence of 0.32%. Newly diagnosed CHB patients (n = 1973; median age 52 years) were followed for a median period of 3.1 years, during which 15% received a CHB treatment. Entecavir was the most common first treatment (66%). During this period, 3.4% of the patients developed compensated cirrhosis (CC), 1.5% decompensated cirrhosis (DC) and 3.0% hepatocellular carcinoma (HCC). Around 43.3% of CHB patients were hospitalized at least once. Hospitalizations, treatment rates, serologic testing and screening for liver diseases increased as the severity of the disease progressed. The average total healthcare cost was 870,568 JPY (7779 USD) per person per year. DC and HCC resulted in the highest management costs. Conclusions: Chronic hepatitis B represents a high clinical and economic burden for patients and caregivers, given its morbidity and associated costs. [ABSTRACT FROM AUTHOR]

Background: Progressive hepatic fibrosis leads to hepatocellular carcinoma (HCC) and decompensated cirrhosis. The aim of this study was to identify the high-risk population for progressive hepatic fibrosis and the incidence of HCC and decompensated cirrhosis in chronic hepatitis B (CHB) patients with antiviral therapy. Methods: The data came from a multicenter, center-randomized, double-blind clinical trial that analyzed only patients in the ETV-treated arm. There was 156 hepatitis B e antigen (HBeAg)-positive and 135 HBeAg-negative patients in 14 institutions. The primary endpoint was fibrosis reversal on 72-week Entecavir (ETV) treatment. The 7-year cumulative incidence of HCC and decompensated cirrhosis were analyzed. Multivariate logistic and LASSO regression analyses were used to screen variables associated with fibrosis reversal. Results: 86/156 (55%) HBeAg-positive and 58/135 (43%) HBeAg-negative patients achieved fibrosis reversal on 72-week ETV treatment. Average age was 43 years, 203 (69.8%) was male, and 144 (49.5%) patients had cirrhosis. Age ≥ 40 years (OR: 0.46, 95% CI 0.23–0.93) and HBcrAg ≥ 8.23 log U/ml (OR: 2.72, 95% CI 1.33–5.54) in HBeAg-positive patients and HBV genotype C (OR: 0.44, 95% CI 0.21–0.97) in HBeAg-negative patients were independent factors of fibrosis reversal. It was confirmed in patients with cirrhosis. After 7-year ETV treatment, seven (4.5%) HBeAg-positive patients occurred HCC or decompensated cirrhosis, including four patients with age ≥ 40 years and six with HBcrAg 8.23log U/ml, while twelve (8.9%) HBeAg-negative patients occurred, including eleven with HBV genotype C. Conclusions: HBeAg-positive patients with a low HBcrAg level or old age, and HBeAg-negative patients with HBV genotype C tended to develop progressive hepatic fibrosis and had a high incidence of HCC and decompensated cirrhosis, even on ETV treatment. [ABSTRACT FROM AUTHOR]

The study enrolled 284 patients with chronic hepatitis B virus infection. Participants included people with mild fibrotic lesions (32.5%), moderate to severe fibrotic lesions (27.5%), cirrhotic lesions (22%), hepatocellular carcinoma (HCC) in 5%, and people with no fibrotic lesions in 13%. Eleven SNPs within DIO2, PPARG, ATF3, AKT, GADD45A, and TBX21 were genotyped by mass spectrometry. The rs225014 TT (DIO2) and rs10865710 CC (PPARG) genotypes were independently associated with susceptibility to advanced liver fibrosis. However, cirrhosis was more prevalent in individuals with the GADD45A rs532446 TT and ATF3 rs11119982 TT genotypes. In addition, the rs225014 CC variant of DIO2 was more frequently found in patients with a diagnosis of HCC. These findings suggest that the above SNPs may play a role in HBV-induced liver damage in a Caucasian population. [ABSTRACT FROM AUTHOR]

Background and Objective: The World Health Organization recommends a universal hepatitis B vaccination within the first 24 h of birth. However, hepatitis B vaccines are given during adolescence in many jurisdictions including in Ontario, Canada. The objective of this study was to assess the cost effectiveness of shifting the hepatitis B vaccination timing from adolescence to birth. Methods: A state-transition model of 18 health states representing the natural history of acute and chronic hepatitis B was developed to conduct a cost-utility analysis. Most input parameters were obtained from the Canadian literature or publicly available provincial data. The model followed a lifetime model time horizon with health outcomes and costs being discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model. Analyses were conducted from a public-payer perspective with all costs adjusted to 2021 Canadian dollars. Results: Hepatitis B vaccination in newborns dominated the current strategy of adolescent vaccination. The probabilistic analysis showed that the newborn strategy was cost effective in 100% of the iterations at a willingness-to-pay threshold of $50,000/quality-adjusted life-year and cost saving in 79.39% of the iterations. A microsimulation projected that a newborn vaccination may lead to reductions in cases by 16.1% in acute hepatitis B, 43.2% in chronic hepatitis B, 48.2% in hepatocellular carcinoma, and 51.9% in hepatitis B liver-related death. Conclusions: Our analysis suggests that changing the age of the hepatitis B vaccination recommendation from adolescent to newborn is cost effective and mostly a cost-saving strategy. Newborn vaccination may lead to cost and health benefits while aligning with best available evidence and guidance from the World Health Organization. [ABSTRACT FROM AUTHOR]

Background: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. Aim: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. Methods: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. Results: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65–0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67–0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02–1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01–1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69–2.83, p < 0.001 vs OR 1.59, 95% CI 1.51–1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98–3.65, p < 0.001 vs OR 1.89, 95% CI 1.76–2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35–7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41–13.20, p = 0.010). Conclusion: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients. [ABSTRACT FROM AUTHOR]

This document discusses the current state of antiviral therapy for chronic hepatitis B (HBV) infection in Japan and the need for innovative therapeutic approaches. The main treatments currently used, interferons and nucleos(t)ide analogs, effectively suppress viral replication but do not fully eliminate viral antigens, increasing the risk of liver cancer progression. The document explores various categories of antiviral drugs targeting HBV, including those that inhibit the sodium taurocholate co-transporting polypeptide (NTCP), disrupt HBV capsid assembly, and have entry and post-entry antiviral activities. It also highlights the development of HBV-RNA inhibitors, specifically targeting HBV-RNAs, which have shown promising results in suppressing HBsAg. The document focuses on the discovery of the HBV replication inhibitor SAG-524, which has been shown to reduce the levels of HBsAg and HBV-DNA through a PAPD5-mediated mechanism. SAG-524 is a potential candidate for functional therapy against HBV and has shown good tolerability. Further preclinical studies are needed before proceeding to clinical trials. [Extracted from the article]