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A hepatitis B or C virus (HBV or HCV) epidemic model with intra- and extra-hepatic coinfection, immune delay and saturation incidence, as well as antiviral therapy is proposed in this paper. The existence of equilibria (infection-free, immune-free and immune-activated), the basic reproduction numbers, i.e., R 0 , R 1 , are given respectively, by which the criteria on (local and global) stability of above equilibria are established. Furthermore, if the immune delay τ > τ 0 , both the existence of subcritical (supercritical) Hopf bifurcation on the immune-activated equilibrium E ∗ , and the stability of bifurcating periodic solutions are obtained. Finally, the theoretical results are demonstrated by numerical simulations. We derive that the immune delay and intra- and extra-hepatic coinfection have significant influence on the transmission of HBV/HCV, could cause more complicated dynamics at E ∗ from stability to unstablity untill bifurcation, which greatly increases the difficulty of disease control. While effective antiviral therapy could evidently decrease the spread of HBV/HCV. [ABSTRACT FROM AUTHOR]

Purpose of Review: In 2016, WHO sets a target to eliminate viral hepatitis as a public health threat by 2030, with significant emphasis placed on reducing MTCT of HBV, which is the leading cause of CHB worldwide. In this review, we discuss the most recent recommendations in the literature on the management of HBV in pregnancy, including treatment considerations during pregnancy and recommendations for infant management, to reduce the MTCT of HBV. Recent Findings: Recent research advancements have focused on further unraveling the safety and efficacy of treatment options during pregnancy, developing more accessible postnatal immunoprophylaxis regimens, and exploring theoretical models for HBV treatment during pregnancy aimed at preventing MTCT. Summary: Despite considerable public health efforts, HBV remains a significant global health concern. Effective collaboration among clinicians is essential for appropriate screening, assessment, treatment during and after pregnancy, and proper follow-up, in order to reduce the MTCT of HBV and optimize maternal health outcomes. [ABSTRACT FROM AUTHOR]

Purpose of Review: Advancements in our understanding of the hepatitis B viral (HBV) life cycle have paved the way for novel approaches to treat HBV infection. This review summarizes the various strategies being pursued to achieve a functional cure, defined as loss of hepatitis B surface antigen (HBsAg) and absence of viral replication 6 months off-therapy. Recent Findings: Direct acting antiviral, host targeting antiviral, and immunological approaches are in various stages of development as treatment for chronic HBV infection. Summary: Novel treatments are being developed in pursuit of a cure for HBV. Current evidence suggests a single therapeutic agent alone may be insufficient, necessitating the need for combination therapy targeting HBV and the host immune response. Ongoing research focused on identifying the best therapeutic combination holds promise in achieving functional cure for HBV. [ABSTRACT FROM AUTHOR]

Purpose of Review: Hepatitis D Virus (HDV), although a small defective virus, poses a substantial public health challenge due to lack of awareness, underrecognized prevalence, and limited treatment options. Universal HDV screening within hepatitis B virus (HBV) cohorts is essential to address this issue. Despite its aggressive nature, effective HDV therapies have remained elusive for over four decades. Recent Findings: Advances in understanding HDV's biology and clinical behavior offer potential therapeutic breakthroughs, fostering optimism. As insights grow, effective and targeted therapies are being developed to improve HDV management. Summary: This review delves into HDV's intricate structure and biology, highlighting formidable hurdles in antiviral development. It emphasizes the importance of widespread screening, exploring noninvasive diagnostics, and examining current and emerging innovative therapeutic strategies. Moreover, the review explores models for monitoring treatment response. In essence, this review simplifies the complexities of effectively combating HDV. [ABSTRACT FROM AUTHOR]

Purpose of Review: Current antiviral therapy effectively suppresses hepatitis B virus (HBV) replication and improves the prognosis. It cannot cure HBV infection. Current clinical guidelines do not advocate universal treatment for all with chronic hepatitis B. However, recent studies are deliberating the expansion of treatment eligibility criteria to encompass those in immune-tolerant, inactive carrier, and gray zone statuses. This review examines the updated information regarding this issue. Recent Findings: For immune-tolerant patients and patients in the gray zone, treatment eligibility might be considered for those with active or significant fibrosis/inflammation, especially those that remain in the immune-tolerant phase older than 30–40. Current evidence does not suggest that antiviral treatment would be beneficial for true inactive carriers. Summary: Evidence-based management is crucial in current antiviral therapy. Appropriate monitoring and evaluation help identify individuals who would benefit from antiviral treatment. Expanding indications may hinge on new evidence or curative therapies with finite durations if available. [ABSTRACT FROM AUTHOR]

Objectives: Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13–30% of the cases, primary HSV-1 leads to the primary herpetic gingivostomatitis (PHGS), often a self-limiting infection; however, it can limit the ability to drink/eat with, sometimes, the need for hospitalization. Multiple therapeutic methods have been proposed. This systematic review aims to collect and critically appraise the available evidence about the clinical management of PHGS. Materials and methods: Literature search including three databases (PubMed, Scopus, Embase), study design, and data analysis were performed following PRISMA guidelines, according to the PICO tool (PROSPERO n° CRD42023391386). Risk of bias was assessed with RoB 2 and ROBINS-I. Results: Five studies on a total of 364 patients (average age: 7.6 years) were identified. The treatment regimens were summarized in acyclovir; acyclovir + honey; fluids and analgesic; maalox + diphenhydramine; lidocaine; chlorhexidine (CHX); CHX + ialuronic acid; CHX + Mucosyte®; antimicrobial photodynamic therapy (aPDT); topical antiviral; topical antiviral + aPDT; and others. Conclusions: Although PHGS is a disease with a high worldwide prevalence, the lack of consensus about therapeutic management indicates gaps in existing evidence. Most of the proposed treatment consists in symptomatic drugs with empiric regimens which are ineffective for the viral replication. The main limit to realize randomized clinical trial is due to the rapid onset and remission of the disease. In fact, the diagnostic delay, estimated in 72 h, decreases the effectiveness of any antiviral drugs. Clinical relevance: Out of the five studies included in this systematic review, only one was able to provide some weak evidence that ACV is an effective treatment, improving healing of oral lesions and reducing duration of symptoms. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of antiviral therapy and drug withdrawal on the incidence of hepatitis B after delivery in pregnant women with chronic hepatitis B virus (CHB) infection who received tenofovir disoproxil fumarate (TDF) treatment. Methods: Eligible CHB pregnant women were enrolled, and received TDF at 32 weeks gestation. The drug was stopped immediately or at 6 weeks after delivery. The HBV biomarkers and clinical biochemical parameters were monitored during gestation and 24 weeks after delivery. Results: There were 264 women completed the observation, including 96 untreated subjects in control group. Among 168 treated subjects, 131 cases stopped drug immediately after delivery and 37 cases delayed the drug withdrawal at 6 weeks after delivery. The incidence of postpartum hepatitis in control, immediate drug withdrawal, and delayed drug withdrawal were 28.1% (27/96), 23.7% (31/131), and 24.3% (9/37), showing no significant difference (χ2 = 0.607, p = 0.738). No factor was found to be associated with the occurrence of postpartum hepatitis. It's noteworthy that 96.3% of postpartum hepatitis in control group and 92.3% of postpartum hepatitis in immediate drug withdrawal group occurred within 12 weeks after delivery. While in delayed drug withdrawal group, the rate of postpartum hepatitis occurred within 12 weeks after delivery was 77.7%. Conclusion: Withdrawing antiviral drug immediately or at 6 weeks after delivery did not affect the incidence of postpartum hepatitis in CHB women, but delaying drug withdrawal might delay the onset of postpartum hepatitis. Clinical trial registration number: NCT03214302. [ABSTRACT FROM AUTHOR]

Background and aims: The formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver is the main cause of persistent hepatitis B virus (HBV) infection. Here, we established highly sensitive and specific methods to detect cccDNA based on CRISPR-Cas13a technology. Methods: We used plasmid-safe ATP-dependent DNase (PSAD) enzymes and HindIII to digest loose circle rcDNA and double-stranded linear DNA, amplify specific HBV cccDNA fragments by rolling circle amplification (RCA) and PCR, and detect the target gene using CRISPR-Cas13a technology. The CRISPR-Cas13a-based assay for the detection of cccDNA was further clinically validated using HBV-related liver tissues, plasma, whole blood and peripheral blood mononuclear cells (PBMCs). Results: Based on the sample pretreatment step, the amplification step and the detection step, we established a new CRISPR-Cas13a-based assay for the detection of cccDNA. After the amplification of RCA and PCR, 1 copy/μl HBV cccDNA could be detected by CRISPR/Cas13-assisted fluorescence readout. We used ddPCR, qPCR, RCA-qPCR, PCR-CRISPR and RCA-PCR-CRISPR methods to detect 20, 4, 18, 14 and 29 positive samples in liver tissue samples from 40 HBV-related patients, respectively. HBV cccDNA was almost completely undetected in the 20 blood samples of HBV patients (including plasma, whole blood and PBMCs) by the above 5 methods. Conclusions: We developed a novel CRISPR-based assay for the highly sensitive and specific detection of HBV cccDNA, presenting a promising alternative for accurate detection of HBV infection, antiviral therapy evaluation and treatment guidance. [ABSTRACT FROM AUTHOR]

Background: Due to stringent reimbursement criteria, significant numbers of patients with compensated cirrhosis (CC) and low-level viremia [LLV; serum hepatitis B virus (HBV)–DNA levels of 20–2000 IU/mL] remain untreated especially in the East Asian countries, despite potential risk of disease progression. We analyzed cost-effectiveness to assess rationales for antiviral therapy (AVT) for this population. Methods: We compared cost and effectiveness (quality-adjusted life years, QALYs) in a virtual cohort including 10,000 54-year-old CC-LLV patients receiving AVT (Scenario I) versus no treatment (Scenario II). A Markov model, including seven HBV-related conditions, was used. Values for transition probabilities and costs were mostly obtained from recent real-world South Korean data. Results: As per a simulation of a base-case analysis, AVT reduced costs by $639 USD and yielded 0.108 QALYs per patient for 5 years among CC-LLV patients compared to no treatment. Thus, AVT is a cost-saving option with lower costs and better effectiveness than no treatment. If 10,000 patients received AVT, 815 incident cases of hepatocellular carcinoma (HCC) and 630 HBV-related deaths could be averted in 5 years compared to no treatment. In case of 10-year observation, AVT was consistently dominant. Even when the transition probabilities from CC-LLV vs. maintained virological response to HCC were same, fluctuation of results also lied within willingness-to-pay in South Korea. In the probabilistic sensitivity analysis with the willingness-to-pay threshold, the probability of AVT cost-effectiveness was 100%. Conclusion: The extended application of AVT in CC-LLV patients may contribute positively to individual clinical benefits and national healthcare budgets. [ABSTRACT FROM AUTHOR]

Background and aim: Antiviral therapy is effective in decreasing disease progression in HBV cirrhosis. However, the long-term effect of antiviral therapy on health-related quality of life (HRQoL) in patients with compensated HBV cirrhosis is unknown. Methods: The patients with compensated HBV cirrhosis enrolled in a randomized controlled trial of entecavir-based therapy were recruited in the present study, if they had HRQoL score at 5-year follow-up or who developed liver-related events (LRE) during follow-up were included. HRQoL was measured with 36-Item Short-Form Health Survey (SF-36) and EuroQol-5D (EQ-5D) at baseline and yearly during follow-up. LRE was defined as the development of decompensation, HCC, or death. Results: A total of 161 patients were included in the present study, with a median age of 48.0 (41.0, 53.0) years, 77.6% being male and 37.2% being HBeAg-positive. During 5 years, 45 patients developed LRE. All eight dimensions of SF-36 were significantly improved after 5 years of antiviral therapy (all p < 0.001), with all dimensions improved more than five points except for physical functioning. Proportion of patients reporting no problems in all five dimensions in EQ-5D increased from 57.8 to 72.0%; visual analogue scale (VAS) and utility index (UI) increased significantly (VAS 79.8 ± 16.4 to 84.4 ± 13.2, UI 0.91 ± 0.13 to 0.95 ± 0.10, both p < 0.001). HRQoL improved or kept stable in the majority of patients who had LRE during follow-up, even stratified by Baveno VI criteria for clinically significant portal hypertension. Conclusion: After 5 years of ETV treatment, HRQoL significantly improved in patients with compensated HBV cirrhosis. (NCT01943617, NCT02849132) [ABSTRACT FROM AUTHOR]