UNASSIGNED: There may be an interaction between viral hepatitis and psychiatric disorders during disease progression. Herein, we conducted Mendelian randomization (MR) to explore the causal associations and mediators between viral hepatitis and psychiatric disorders.
UNASSIGNED: Genome-wide association studies summary data for viral hepatitis [including chronic hepatitis B (CHB) and chronic hepatitis C (CHC)] and psychiatric disorders (including depression, anxiety, schizophrenia, obsessive-compulsive disorder, bipolar disorder, and post-traumatic stress disorder) were obtained. Two-sample MR was performed to assess the causal associations between viral hepatitis and psychiatric disorders. Further, a mediation analysis was conducted to evaluate the potential mediators. Inverse-variance weighted, MR-Egger, and weighted median were used as the main methods, while a sensitivity analysis was performed to evaluate pleiotropy and heterogeneity.
UNASSIGNED: There was no causal effect of CHB/CHC on psychiatric disorders, as well as psychiatric disorders on CHB. However, schizophrenia presented a causal effect on increased CHC risk [odds ratio (OR)=1.378, 95%CI: 1.012-1.876]. Further, a mediation analysis identified coffee consumption and body mass index as mediators in the effect of schizophrenia on CHC, mediating 3.75% (95%CI: 0.76%-7.04%) and 0.94% (95%CI: 0.00%-1.70%) proportion, respectively.
UNASSIGNED: We revealed that schizophrenia patients faced a high risk of CHC, and insufficient coffee consumption and underweight could mediate the causal effect of schizophrenia on CHC. The prevention of hepatitis C might be a beneficial strategy for patients with schizophrenia. The right amount of nutrition supplements and coffee consumption might be part of a beneficial lifestyle in preventing the high CHC risk in patients with schizophrenia.

Diagnosis and treatment of hepatitis B virus (HBV) infection in children is a hotspot of concern in the field of HBV infection. This article reviews the current status and progress of antiviral treatment for children with chronic hepatitis B (CHB) in recent years, focusing on clinical issues such as the choice of antiviral treatment regimen for children with HBeAg-positive CHB (immune-clearance phase), the necessity of antiviral treatment for children with HBeAg-positive HBV infection (immune-tolerance phase), and the timing of antiviral treatment for infants with HBV infection, to explore the relevant factors that may affect the clinical cure of children with CHB. At the same time, based on the expert consensus on the prevention and treatment of children with CHB just published by Chinese experts, relevant diagnosis and treatment plans are proposed, with a view to providing reference and basis for clinical decision-making in children with CHB.
儿童HBV感染的诊治是乙型肝炎领域的关注热点，该文就近年来儿童慢性乙型肝炎的抗病毒治疗现状与进展进行综述，围绕HBeAg阳性慢性乙型肝炎（又称免疫清除期）儿童抗病毒治疗方案选择、HBeAg阳性HBV感染（又称免疫耐受期）儿童抗病毒治疗的必要性和婴儿HBV感染者的抗病毒治疗时机等临床问题，探讨可能影响儿童慢性乙型肝炎临床治愈的相关因素；同时依据我国专家刚刚发表的《儿童慢性乙型肝炎防治专家共识》，提出了相关的诊疗方案，以期为儿童慢性乙型肝炎的抗病毒治疗决策提供科学依据。.

OBJECTIVE: Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long-term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real-world setting.
METHODS: A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression.
RESULTS: In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05).
CONCLUSIONS: These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long-term outcomes of patients with CHB in the Japanese population.

BACKGROUND: Observational studies have indicated a link between autoimmune liver diseases (AILD) and chronic hepatitis B (CHB) through observational studies. The association between AILD and CHB remains indeterminate.
METHODS: A two-sample Mendelian randomization (MR) analysis was conducted to scrutinize the causal nexus between AILD and CHB utilizing summary statistics derived from extensive genome-wide association studies (GWASs) in European populations. The primary statistical methodology employed was the inverse variance-weighted (IVW) method to deduce the causal connection of AILD on CHB. This study incorporated primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) as subtypes of AILD. Additionally, we conducted a multivariable MR (MVMR) analysis to account for the potential confounding effects of smoking, alcohol consumption, body mass index (BMI), and some autoimmune diseases.
RESULTS: Our MR investigation encompassed a cohort of 725,816 individuals. The MR analysis revealed that genetically predicted PSC significantly correlated with a reduced risk of CHB (IVW OR = 0.857; 95%CI: 0.770-0.953, P = 0.005). Conversely, the reverse MR analysis suggested that genetic susceptibility to PSC might not modify the risk of CHB (IVW OR = 1.004; 95% CI: 0.958-1.053, P = 0.866). Genetically proxied PBC and AIH exhibited no discernible causal association with CHB in the MR analysis using the IVW method (P = 0.583; P = 0.425). The MVMR analysis still indicated a decreased risk of CHB associated with PSC (OR = 0.853, P = 0.003).
CONCLUSIONS: Our study elucidates a causal relationship between PSC and a diminished risk of CHB.

OBJECTIVE: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection.
METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery.
RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices.
CONCLUSIONS: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

UNASSIGNED: The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR).
UNASSIGNED: Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran\'s Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis.
UNASSIGNED: MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran\'s Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust.
UNASSIGNED: CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies, including cancer chemotherapy. HBV reactivation can cause significant morbidity and even mortality, which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.
OBJECTIVE: To determine the prevalence of chronic HBV (CHB) and occult HBV infection (OBI) among oncology and hematology-oncology patients undergoing chemotherapy.
METHODS: In this observational study, the prevalence of CHB and OBI was assessed among patients receiving chemotherapy. Serological markers of HBV infection [hepatitis B surface antigen (HBsAg)/anti-hepatitis B core antigen (HBc)] were evaluated for all patients. HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.
RESULTS: The prevalence of CHB in the study cohort was determined to be 2.3% [95% confidence interval (95%CI): 1.0-4.2]. Additionally, the prevalence of OBI among the study participants was found to be 0.8% (95%CI: 0.2-2.3).
CONCLUSIONS: The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy. Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection, which can lead to increased morbidity and mortality.

BACKGROUND: Preventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB.
METHODS: We analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months.
RESULTS: Twenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10- 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2-10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001-0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240-21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value.
CONCLUSIONS: In CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.

Integration of hepatitis B virus (HBV) DNA into the human genome is recognized as an oncogenic factor and a barrier to hepatitis B cure. In the study, biopsy liver tissues were collected from adolescents and young adults with acute HBV infection younger than or equal to 35 years of age and from HBV-infected infant patients younger than or equal to 6 months of age. A high-throughput sequencing method was used to detect HBV DNA integration. Totally, 12 adolescents, young adults, and 6 infants were included. Among the 12 patients with acute HBV infection, immunohistochemical staining of intrahepatic hepatitis B surface antigen for all displayed negative results, and no HBV DNA integrants in the hepatocyte DNA were confirmed. All infant patients had elevated levels of alanine aminotransferase and high levels of serum HBV DNA. Numerous gene sites of hepatocyte DNA were integrated by HBV DNA for each infant patient, ranging from 120 to 430 integration sites. The fragile histidine triad gene was the high-frequency integrated site in the intragenic region for infant patients. In conclusion, hepatocyte DNA is integrated by HBV DNA in babies with active hepatitis B but seems seldom affected among adolescents and young adults with acute HBV infection. Infantile hepatitis B should be taken seriously considering abundant HBV DNA integration events.

UNASSIGNED: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics (PK), and antiviral activity of three doses of EDP-514 in treatment naïve viremic patients with HBeAg-positive or -negative chronic HBV infection.
UNASSIGNED: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days.
UNASSIGNED: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were 2.9, 3.3, 3.5 and 0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was 2.9, 2.4, 2.0, and 0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events (TEAEs) of mild or moderate severity with no discontinuations, serious AEs or deaths.
UNASSIGNED: In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.