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Background: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. Results: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. Conclusions: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study. [ABSTRACT FROM AUTHOR]

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

Aim Methods Results Conclusions Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core‐related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15.Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB‐4 index, alpha‐fetoprotein and gamma‐glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma‐glutamyl transpeptidase ≥22 U/L, FIB‐4 index ≥1.93, and GDF‐15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10‐year HCC cumulative incidence rates were 0% and 41.0%, respectively.High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs. [ABSTRACT FROM AUTHOR]

Objectives: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is frequently preceded by infections. The underlying pathomechanism, however, remains poorly understood. Here, we present the clinical data of two MOGAD patients with concurrent syphilis infection and investigate the reactivity of patient-derived antibodies to MOG and Treponema pallidum (T. pallidum). Methods: Longitudinal serumsamples and soluble immunoglobulins in single B cell supernatants were measured for MOG reactivity by a live cell-based assay. Reactivity against T. pallidum was assessed by enzyme-linked immunosorbent assay. Results: The two patients presented MOGAD and concurrent latent syphilis infection, manifesting as cervical myelitis and unilateral optic neuritis, respectively. The first patient had been living with HIV on antiretroviral therapy, and the second was concomitantly diagnosed with chronic hepatitis B infection. Upon screening of B cell supernatants, we identified reactivity to MOG or T. pallidum. Notably, one B cell showed reactivity to both antigens. Discussion: The coexistence of MOGAD diagnoses and latent syphilis, alongside the identification of antibody reactivity to MOG and T. pallidum, underscores the potential pathomechanistic link between syphilis infection and subsequent autoimmune neuroinflammation. Cross-reactivity between MOG and T. pallidum antibodies remains to be validated on a molecular level, and further characterization of infectious triggers associated with MOGAD is needed. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo-electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D2- and D4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions. [ABSTRACT FROM AUTHOR]

Bepirovirsen is a developmental antisense oligonucleotide (ASO) for treatment of chronic hepatitis B virus infection. No pharmacokinetic (PK) studies comparing participants with hepatic impairment (HI) and healthy participants (HPs) have been conducted with ASOs. Given the target patient population, characterization of bepirovirsen PK in HI was imperative. This phase 1, nonrandomized, open‐label study (NCT04971928) evaluated the PKs of a single 300‐mg dose of bepirovirsen in participants with HI and matched HPs, enrolled in 2 parts (Part 1: moderate HI; Part 2: mild HI). If no predefined difference in the area under the concentration‐time curve from time 0 (predose) to infinite time (AUC0‐∞) and maximum observed concentration (Cmax; geometric mean ratio [GMR] 0.5‐1.5) was identified in Part 1, findings were applied to mild HI, eliminating Part 2. Participants were monitored for 50 days post‐treatment and noncompartmental analysis estimated PK parameters. Twenty‐four participants (moderate HI, n = 12; HP, n = 12) received bepirovirsen and completed Part 1. AUC0‐∞ and Cmax were lower in participants with moderate HI (GMR 0.69 and 0.67, respectively) than in HPs, while apparent clearance (CL/F) and apparent terminal phase volume of distribution (Vz/F) were higher (GMR 1.44 and 1.64, respectively), but fell within the predefined thresholds of difference for this study. Part 2 was omitted. Adverse events were mild. Moderate HI did not have a clinically relevant impact on bepirovirsen PK or safety. [ABSTRACT FROM AUTHOR]

ABSTRACT Enhanced liver fibrosis (ELF) score is a noninvasive assessment for liver fibrosis. We aimed to evaluate the performance of changes in ELF score 3 years apart in combination with liver stiffness measurement (LSM)‐hepatocellular carcinoma (HCC) score to predict HCC in chronic hepatitis B (CHB) patients. This is a prospective cohort study. Patients who underwent transient elastography (TE) examinations and at intermediate or high risk of HCC defined by LSM‐HCC score were invited to repeat the examination about 3 years later. Their serum samples at these two time points were retrieved to assess the ELF score changes. The primary endpoint was HCC. There were 445 CHB patients (males: 73.9%; mean age: 51.6 ± 10.3 years) who received two TE examinations and ELF scores. Among them, 252 (56.6%) and 193 (43.4%) patients were at intermediate and high HCC risk at first assessment defined by LSM‐HCC score, respectively. Kaplan–Meier analysis showed that the changes in ELF score could stratify the HCC risk in both intermediate‐ and high‐risk patients defined by LSM‐HCC score (p < 0.001 for intermediate‐risk group; p = 0.011 for high‐risk group). Patients remained having mild or moderate fibrosis at both assessments had the lowest risk of HCC (4.0%), followed by patients with fibrosis regressed (11.3%; p = 0.014) during a mean follow‐up of 163 months. Patients remained having or progressed to severe fibrosis were at highest risk of HCC (>20%). Consistent findings were demonstrated in patients at both intermediate and high risk of HCC defined by LSM‐HCC score. Dynamic changes in ELF score provided additional value to LSM‐HCC score for stratifying HCC risk in CHB patients. [ABSTRACT FROM AUTHOR]

Background: The Aboriginal health workforce has unique insights given their healthcare experience and interactions with their communities. The aims of this project were to explore their perceptions of hepatitis B related shame and ways to improve hepatitis B care in Aboriginal and Torres Strait Islander communities of Northern Territory's Top End, Australia. Methods: We conducted a qualitative study with guidance from the Menzies School of Health Research Infectious Diseases Indigenous Reference Group. The Aboriginal health workforce was asked to participate in semi-structured interviews exploring hepatitis B related shame and ways to improve hepatitis B care. Qualitative data were evaluated using reflexive thematic analysis. Results: There were fifteen semi-structured interviews with participants representing eight different communities. The experience of shame was reported by the Aboriginal health workforce to be common for individuals diagnosed with hepatitis B and comprised feelings of fear related to transmitting the virus, to being isolated, and to being at fault. Shame was mediated by poor health literacy, communication, the lack of culturally safe spaces and was perpetuated by intersecting stereotypes. Improvements in care can be achieved by utilising the Aboriginal health workforce more effectively, improving communication and the availability of culturally safe spaces, emphasising community connection, and reframing hepatitis B as a chronic condition. Conclusions: Hepatitis B related shame was an important issue and impactful in Aboriginal and Torres Strait Islander communities in the Top End of the Northern Territory. There were many facets to shame in these communities and it was mediated by several factors. The Aboriginal health workforce has emphasised several pathways to improve care and diminish the impact of shame, such as improving communication and the availability of culturally safe spaces. [ABSTRACT FROM AUTHOR]

ABSTRACT Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow‐up data was retrieved in 7833 antiviral‐treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB‐infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death‐1 (PD‐1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV‐specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFβ) production in undepleted PBMCs and Treg‐depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow‐up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57–0.87). PD‐1 expression was increased in CD4+T cells, CD8+T cells and CD20+B cells among smokers compared to non‐smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV‐specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non‐smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD‐1 expression on lymphocytes, and impairment of effector functions of HBV‐specific T cells in CHB. [ABSTRACT FROM AUTHOR]

This document contains a collection of four case reports that provide insights into various liver diseases. The first report focuses on the prevalence of intestinal failure-associated liver disease (IFALD) in patients receiving long-term home parenteral nutrition (HPN), identifying ongoing HPN and short gut syndrome as predictors for IFALD. The second report introduces a predictive model called the Portal Decompensation Score (PDS), which accurately predicts portal hypertension-related decompensation events in cirrhosis patients. The third report describes a quality improvement project aimed at enhancing the assessment of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes in primary care. Lastly, the fourth report presents a case of hepatosplenic candidiasis in a non-neutropenic patient following endoscopic cholangiopancreatography (ERCP). These case reports offer valuable information on the diagnosis, management, and outcomes of different liver diseases. [Extracted from the article]

Background: Most Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine blood donor screening for HBV infection since 2015, and a few centers upgraded MP to individual donation (ID) NAT screening recently, raising urgent need for cost-benefit analysis of different screening strategies. In an effort to prevent transfusion-transmitted infections (TTIs) for HBV, cost-benefit analyses of three different screening strategies: HBsAg alone, HBsAg plus MP NAT and HBsAg plus ID NAT were performed in blood donors from southern China where HBV infection was endemic. Methods: MP-6 HBV NAT and ID NAT were adopted in parallel to screen blood donors for further comparative analysis. On the basis of screening data and the documented parameters, the number of window period (WP) infection, HBV acute infection, chronic hepatitis B infection (CHB) and occult hepatitis B infection (OBI) was evaluated, and the potential prevented HBV TTIs and benefits of these three strategies were predicted based on cost-benefit analysis by an estimation model. Results: Of 132,323 donations, the yield rate for HBsAg-/DNA + screened by ID NAT (0.12%) was significantly higher than that by MP NAT (0.058%, P < 0.05). Furthermore, the predicted transfusion-transmitted HBV cases prevented was 1.25 times more by ID NAT compared to MP-6 NAT. The cost-benefit ratio of the universal HBsAg screening, HBsAg plus ID NAT and HBsAg plus MP NAT were 1:58, 1:27 and 1:22, respectively. Conclusions: Universal HBsAg ELISA screening in combination with HBV ID NAT or MP-6 NAT strategies was highly cost effective in China. To further improve blood safety, HBsAg plus HBV DNA ID NAT screening should be considered in HBV endemic regions/countries. [ABSTRACT FROM AUTHOR]