Multiomics Analyses Reveal that Fatty Acid Metabolism and TCA Cycle Contribute to the Achievement of Functional Cure in Chronic Hepatitis B.

Peg-IFNα is one of the current therapeutic strategies for Hepatitis B virus (HBV) seroclearance. Nevertheless, the underlying mechanisms are not yet adequately understood. The objective of this study was to explore the potential mechanisms using multiomics approach.

S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella-based tumor therapy and host defense.

Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection.

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Objective: We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).

Methods: MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes.

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

Background & Aims: The changes in HBV-specific B cells in patients with chronic hepatitis B (CHB) undergoing pegylated interferon-α (PEG-IFNα) treatment and achieving functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B cells.

Methods: We included 39 nucleos(t)ide analogue-treated patients with CHB who received sequential combination therapy with PEG-IFNα and eight treatment-naïve patients.

Characterization of BCP/PreC/C region quasispecies in treatment-naive patients with different phases of HBV infection using next-generation sequencing.

Background: To analysis of quasispecies (QS) changes and high-frequency mutations in the BCP/PreC/C region of patients at different phases of hepatitis B virus (HBV) infection and provides novel biomarkers for the diagnosis of chronic hepatitis B (CHB) patients.

Methods: With the application of next-generation sequencing technology, we were able to sequence the HBV BCP/PreC/C regions in 40 patients, each at different phases of the HBV infection. The heterogeneity of QS and the frequency of mutations were calculated using MEGA 7 software.

A novel microfluidic chip-based digital PCR method for enhanced sensitivity in the early diagnosis of colorectal cancer via mSEPT9.

Background: To enhance the sensitivity of plasma methylated Septin9 gene (mSEPT9) detection in colorectal cancer (CRC) screening, we developed a microfluidic chip-based digital PCR (dPCR) method suitable for low-concentration samples, aiming to apply it for mSEPT9 detection in CRC diagnosis.

Methods: Our microfluidic chip-based dPCR method utilized specific primers and probes with locked nucleic acids (LNAs) modifications for mSEPT9 detection. We evaluated its performance, including detection limit, specificity, and linear range, comparing it with a commercial qPCR reagent kit using the same samples (95 CRC, 23 non-CRC).

Detection of serum large and middle hepatitis B virus surface proteins: A novel potential diagnostic and prognostic biomarker for chronic hepatitis B.

Background: The significance of large (LHB) and middle (MHB) HBV surface proteins in chronic hepatitis B (CHB) remains uncertain. This study investigates the role of LHB and MHB in different infection phases and liver diseases.

Methods: Serum samples from 217 patients with HBV chronic infection, CHB, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) were subjected to quantification of LHB and MHB using ELISA.

A novel gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B.

Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5.

Oncostatin M Induces IFITM1 Expression to Inhibit Hepatitis B Virus Replication Via JAK-STAT Signaling.

Background & Aims: Functional cure is achieved by a limited number of patients with chronic hepatitis B (CHB) after nucleotide analogue(s) and interferon treatment. It is urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti-hepatitis B virus (HBV) potency of interleukin-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency.

Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection.

Objective: Hepatitis B virus (HBV) infection causes substantial harm to mitochondrial activity, which hinders the development of effective treatments for chronic hepatitis B (CHB). The discovery of the mitochondrial-derived short peptide MOTS-c, which possesses multiple bioactivities, offers a promising new approach in treating HBV infection. This study aims to explore the diagnostic and therapeutic potential of MOTS-c in HBV-related diseases and its molecular mechanism.

IFIT3 Is Increased in Serum from Patients with Chronic Hepatitis B Virus (HBV) Infection and Promotes the Anti-HBV Effect of Interferon Alpha via JAK-STAT2 .

Increasing evidence indicates that interferon alpha (IFN-α) therapy is an effective treatment option for a subgroup of patients with chronic hepatitis B virus (HBV) infection. It has been confirmed that interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), a member of the interferon-stimulated genes (ISGs), could inhibit the replication of various viruses. However, its effect on HBV replication is unclear.

Photodynamic therapy-improved oncolytic bacterial immunotherapy with FAP-encoding S. typhimurium.

Genetically engineered bacterial cancer therapy presents several advantages over conventional therapies. However, the anticancer effects of bacterium-based therapies remain insufficient, and serious side effects may be incurred with the increase in therapeutic dosages. Photodynamic therapy (PDT) suppresses tumor growth by producing reactive oxygen species (ROS) through specific laser-activated photosensitizers (PSs).

Using machine learning models to predict HBeAg seroconversion in CHB patients receiving pegylated interferon-α monotherapy.

Background And Objective: Though there are many advantages of pegylated interferon-α (PegIFN-α) treatment to chronic hepatitis B (CHB) patients, the response rate of PegIFN-α is only 30 ~ 40%. Therefore, it is important to explore predictors at baseline and establish models to improve the response rate of PegIFN-α.

Methods: We randomly divided 260 HBeAg-positive CHB patients who were not previously treated and received PegIFN-α monotherapy (180 μg/week) into a training dataset (70%) and testing dataset (30%).

Adenosine Triphosphate in Serum as a Promising Biomarker for Differential Diagnosis of Hepatitis B Disease Progression.

The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection.

Proteomic characterization of the natural history of chronic HBV infection revealed by tandem mass tag-based quantitative proteomics approach.

Currently, determining when to start antiviral therapy in patients with chronic HBV infection is a controversial issue. One crucial reason is that biomarkers for distinguishing the natural history of chronic HBV infection are unmet needs. In this study, we aimed to explore novel biomarkers and therapeutic targets for the diagnosis and treatment of chronic HBV infection by using tandem mass tag (TMT)-based quantitative proteomics approach.

Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8 T and NK cell function.

Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients.

IL-17 and IL-21 polymorphisms in relation to HBV related hepatocellular carcinoma in Chinese Han population.

Objective: Inflammatory cytokine gene polymorphisms may influence the hepatic and extrahepatic HBV-related disease. In this study, we aimed to investigate the relationship between polymorphisms of IL-17, IL-21 gene and HBV related hepatocellular carcinoma in Chinese Han population.

Methods: We performed a multi-center study comprised 866 HBV-related hepatocellular carcinoma (HCC) patients and 1086 unrelated patients with a diagnosis of chronic hepatitis B (CHB) as control to evaluate the effects of IL-17 (rs4711998), IL-21 SNPs (rs12508721, rs13143866 and rs2221903) and the susceptibility of HCC.

The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway.

The ability to harness innate immunity is a promising solution for improving cancer immunotherapy. Interferon (IFN) induces expression of IFN-stimulated genes (ISGs) by activating the JAK-STAT signaling pathway to promote innate immunity and inhibit malignant tumor growth, but the functions and mechanisms of most ISGs in cancer regulation are unknown. As an innate immune effector, ISG12a promotes the innate immune response to viral infection.

IRF1 Promotes the Innate Immune Response to Viral Infection by Enhancing the Activation of IRF3.

Innate immunity is an essential way for host cells to resist viral infection through the production of interferons (IFNs) and proinflammatory cytokines. Interferon regulatory factor 3 (IRF3) plays a critical role in the innate immune response to viral infection. However, the role of IRF1 in innate immunity remains largely unknown.

The efficacy of addition of Tenofovir Disoproxil Fumarate to Peg-IFNα-2b is superior to the addition of Entecavir in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone.

There are limited data regarding the efficacy of addition of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to Peg-IFNα-2b in HBeAg positive chronic hepatitis B (CHB) patients without early response to Peg-IFNα-2b. In this study, we aimed to evaluate the efficacy of ETV and TDF in HBeAg positive CHB patients who had a poor response to Peg-INFα-2b at the end of 12 weeks of monotherapy. A total of 40 HBeAg-positive CHB patients who were naive to antiviral therapy were recruited.

Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients.

Background And Aim: Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients.

Methods: The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated.

Establishment of Coamplification at Lower Denaturation Temperature PCR/Fluorescence Melting Curve Analysis for Quantitative Detection of Hepatitis B Virus DNA, Genotype, and Reverse Transcriptase Mutation and Its Application in Diagnosis of Chronic Hepatitis B.

Dynamic and real-time hepatitis B virus (HBV) DNA, genotype, and reverse transcriptase mutation analysis plays an important role in diagnosing and monitoring chronic hepatitis B (CHB) and in assessing the therapeutic response. We established a highly sensitive coamplification at lower denaturation temperature PCR (COLD-PCR) coupled with probe-based fluorescence melting curve analysis (FMCA) for precision diagnosis of CHB patients. The imprecision with %CV and detection limit of HBV DNA detected by COLD-PCR/FMCA were 2.

Sam68 Promotes Hepatitis C Virus Replication by Interaction with Stem-Loop 2 of Viral 5' Untranslated Region.

The Src-associated in mitosis 68-kDa (Sam68) protein is a highly conserved nuclear protein and is involved in a series of cellular processes, including transcription and signal transduction. Sam68 is comprised of 443 amino acids and contains an RGG box domain, a KH domain, and a tyrosine-rich domain. Its role in hepatitis C virus (HCV) replication is unknown.