BACKGROUND

The World Health Organization (WHO) estimates that in 2015, approximately 325 million or 4.4% of the global population were living with chronic hepatitis B or hepatitis C infection. In the same year, around 1.34 million died from this disease.

This study aimed to estimate the burden of hepatitis B in the Philippines and to determine the costeffectiveness of possible interventions.

This study utilized the Center for Disease Analysis Foundation’s (CDAF’s) mathematical disease burden model of hepatitis B. Model inputs were collected using literature review, key informant interviews, expert panel interviews, and records review, and were validated through a series of round table discussions with experts.

Results show that in 2017, the prevalence of chronic hepatitis B infection in the Philippines was 9.7%, equivalent to 10 million infected individuals. Although the model projects a decreasing trend in chronic hepatitis B virus (HBV) infections, liver-related mortality and morbidity due to these viruses are expected to rise if the status quo is maintained. Results show that substantial increase in government subsidy for WHO elimination scenarios would be required to achieve cost-effective outcomes.

Hepatitis B remains a huge problem in the Philippines. The HBV modelling exercise reveal that it will be worthwhile and cost-effective to adhere to the WHO elimination targets. A substantial financial investment will be necessary to do so, specifically a significant scale up in the screening, diagnosis, treatment, and monitoring of patients with HBV. While this modelling exercise does not yield burden of disease as accurate as a prevalence survey, experts consulted in the round table discussions agreed with the modelling inputs.

BACKGROUND AND OBJECTIVE

Stigma remains a profound barrier to public health, particularly in managing diseases such as Hepatitis B, which is highly prevalent in hyperendemic regions like the Philippines. The social stigma associated with such health conditions can severely limit access to care and hinder adherence to treatment, exacerbating the overall disease burden. Despite the critical impact of stigma on health outcomes, there is a notable gap in the systematic evaluation of the tools used to measure stigma related to health conditions like Hepatitis B. This study aims to fill this gap by reviewing existing instruments for their methodologies, reliability, and validity to inform the development of a refined tool tailored to the Philippine context.

A systematic search was conducted across six databases, including PubMed, Cochrane Database of Systematic Reviews, Open Grey, DissOnline, Philippine Health Research Registry (PHRR), and Health Research and Development Information Network (HERDIN), following PRISMA guidelines. The search strategy focused on identifying quantitative and mixed-methods studies using questionnaires to measure HBV-related stigma and discrimination. Studies published between January 1, 1992, and December 31, 2023, were considered. The selection process involved screening for duplicates, reviewing titles and abstracts, and performing a full-text review based on predetermined eligibility criteria.

The initial search yielded 1,198 articles, with 24 duplicates removed. After title and abstract screening, 28 articles were considered for full-text review, resulting in 17 relevant articles in the final analysis with 15 unique instrumentations. The majority of studies employed cross-sectional designs (n=8), with a significant concentration in Asian countries (n=11), indicating a regional focus in HBV stigma research. The review identified a range of questionnaire methodologies, but most studies lacked specificity regarding the type of stigma measured. The Likert Scale was the most commonly used measurement tool, yet few studies provided cut-off values for stigma levels. Validity and reliability testing was reported in 12 articles, including pilot studies, Cronbach’s alpha, and factor analysis.

The lack of a universal methodology and specificity in existing instruments underscores the importance of developing a refined tool that can accurately capture the nuances of stigma and discrimination associated with HBV. The urgent need for standardized, reliable, and culturally sensitive questionnaires is evident, underscoring their importance in developing effective public health strategies and improving treatment outcomes for individuals living with HBV, especially in the Philippines.

BACKGROUND

The Philippines is hyperendemic for hepatitis B infection. Vaccination is crucial for protection. Local data on the antibody response after completion of the primary vaccination series is limited.

This study aimed to measure the anti-HBs levels among college students who completed primary hepatitis B vaccination series, compare seropositivity across stratified groups and correlate anti-HBs levels with the time elapsed since the last vaccine dose.

This cross-sectional study included 111 college students in health-related courses with immunization record showing the complete primary Hepatitis B vaccination series. Participants were stratified based on the following vaccination schedules: 0-1-6-month group; 0-1-2-month group; and booster group. Anti-HBs titers were determined.

Statistical analyses included One-way ANOVA, Kruskal-Wallis test, Fisher’s Exact test and Shapiro-Wilk normality test. Kaplan-Meier Survival Estimate assessed the probability of anti-HBs seropositivity over time. Data were analyzed using STATA 13.1.

The baseline characteristics of the study population were homogenous. The median anti-HBs titer several years after primary vaccination was low at 2.9 mIU/mL. Participants in the booster group had the highest seropositivity rate (57.14%) with a median titer of 30.16 mIU/mL. There was an inverse relationship between anti-HBs titer and elapsed time since the last vaccine dose. Kaplan-Meier Survival Estimate showed that the seropositivity decreases to 90.56% after 15.8 years, 51.3% after 17.5 years, and 2.97% at 18 years.

This study revealed low anti-HBs titers among students who previously completed primary vaccination series, with no significant difference between two schedules. Booster doses resulted in the highest seropositivity. Over-all, seropositivity declines over time.

Pemphigus is a rare, chronic, life-threatening autoimmune blistering disease characterized by blisters and erosions of the skin and mucous membranes. Rituximab has been approved as a first-line treatment for moderate to severe pemphigus vulgaris. Despite of its efficacy in achieving remission, Rituximab can also lead to serious complications such as Hepatitis B reactivation.

We present a case of a 42-year-old Filipino male with severe pemphigus vulgaris on chronic immunosuppressive therapy. He had a 10-month history of multiple bullae and crusted erosions associated with pruritus and burning pain on the mouth resulting to odynophagia and dysphagia. He is a known case of chronic Hepatitis B with unrecalled vaccination status. On physical examination, Nikolsky and Asboe-Hansen signs were positive. Histopathology show intraepidermal split and row of suprabasal keratinocytes pattern. ELISA showed very high levels (>200 RU/ml) for both anti-desmoglein 1 & 3. DIF was positive for IgG & C3. Prior to Rituximab administration, Tenofovir 300 mg/tab/day was started as pre-emptive therapy. To lessen the dependence on systemic corticosteroids, two infusions of Rituximab 1g 2 weeks apart were then given. Notable improvement was seen, evidenced by absence of new bullae, reduction of affected BSA, from 19% to 5.3% and decreased PDAI (78 to 1) and ABSIS (46.5 to 2.75) four months after treatment. Maintained remission and undetectable Hepatitis B viral load 4 months following the last dose of Rituximab were noted, indicating a positive treatment response to both Rituximab and Tenofovir.

Rituximab represents a viable treatment option even for patients with chronic Hepatitis B. Pre-emptive therapy may be done prior to infusion to prevent hepatitis reactivation. Clinical evidence supports the efficacy and safety of Rituximab in this case where preventive measures are taken.

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.
Humans ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B/drug therapy* ; Hepatitis B virus ; Antiviral Agents/therapeutic use* ; Gastroenterology

Objective:b> T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods:b> Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results:b> Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion:b> There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.
Humans ; Hepatitis B virus ; Acute-On-Chronic Liver Failure/pathology* ; Hepatitis B, Chronic ; T-Lymphocyte Subsets/pathology* ; Receptors, Immunologic

Objective:b> To analyze the hepatic pathological characteristics and factors influencing an alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B (CHB) and further explore the optimal ALT threshold strategy for initiating antiviral therapy. Methods:b> Clinical data of treatment-naïve CHB patients who underwent liver biopsies from January 2010 to December 2019 were retrospectively collected. Multiple regression models were used to explore the ALT levels and significant risk of hepatic histological changes (≥G2/S2). Receiver operating characteristic curve was used to evaluate the value of different models in diagnosing liver tissue inflammation≥G2 or fibrosis ≥ S2. Results:b> A total of 447 eligible CHB patients, with a median age of 38.0 years and 72.9% males, were included. During ALT normalization, there was significant liver inflammation (≥G2) and fibrosis (≥S2) in 66.9% and 53.0% of patients, respectively. With an ALT rise of 1-2×ULN, the proportions of liver inflammation≥G2 and fibrosis≥S2 were 81.2% and 60.0%, respectively. After adjusting for confounding factors, higher ALT levels (> 29 U/L) were found to be associated with significant liver inflammation (OR: 2.30, 95% CI: 1.11 ~ 4.77) and fibrosis (OR: 1.84, 95% CI: 1.10 ~ 3.09). After the measurement of glutamyltransferase-platelet ratio (GPR), the proportion of CHB patients with≥G2/S2 was significantly reduced under different treatment thresholds of ALT standards, and in particular, the erroneous evaluation of liver fibrosis≥S2 was significantly improved (33.5% to 57.5%). Conclusion:b> More than half of CHB patients have a normal ALT or one within 2 × ULN, regardless of whether or not there is apparent inflammation and fibrosis. GPR can significantly improve the precise assessment of different conditions of treatment thresholds for the ALT value in CHB patients.
Male ; Humans ; Adult ; Female ; Hepatitis B, Chronic/complications* ; Alanine Transaminase ; Retrospective Studies ; Liver/pathology* ; Liver Cirrhosis/complications* ; Inflammation/pathology* ; Hepatitis B e Antigens

Objective:b> To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods:b> Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results:b> 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion:b> The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.
Humans ; Male ; Female ; Hepatitis B, Chronic/drug therapy* ; Liver Cirrhosis/pathology* ; Elasticity Imaging Techniques ; Antiviral Agents/therapeutic use* ; Liver/pathology*

Objective:b> To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods:b> Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results:b> 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion:b> Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/pathology* ; alpha-Fetoproteins/metabolism* ; Biomarkers ; Hepatitis B ; ROC Curve ; Glycoproteins ; Biomarkers, Tumor

The resolution of the hepatitis C issue has raised expectations for a chronic hepatitis B cure, driving the industry to expand investment in research and development efforts to strengthen functional cure strategies. These strategies have a wide variety of types, and the published research findings are heterogeneous. The theoretical analysis of these strategies is of great significance for determining prioritized research orientations as well as sensibly allocating research and development resources. However, due to a paucity of necessary conceptual models, current theoretical analysis has not been able to unify various therapeutic strategies into a proper theoretical framework. In view of the fact that the decrease in the quantity of cccDNA is an inevitable core event accompanied by the process of functional cure, this paper intends to analyze several chronic hepatitis B cure strategies using cccDNA dynamics as a framework. Furthermore, there are currently few studies on the dynamics of the cccDNA field, hoping that this article can promote recognition and research in this field.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/therapeutic use* ; Virus Replication ; DNA, Circular/therapeutic use* ; DNA, Viral/genetics* ; Hepatitis B/drug therapy*