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.

Hepatitis B virus biomarkers are mainly used in clinical practice to diagnose infection, monitor disease progression, evaluate response to chronic hepatitis B treatment, and evaluate the efficacy of novel antiviral drugs in clinical trials. In combination with the recent research progress of antiviral therapy for chronic hepatitis B and the actual needs of clinical diagnosis and treatment, the expert consensus was formulated by the Cooperative Group of Basic Research and Experimental Diagnosis of Liver Diseases, Chinese Society of Hepatology, Chinese Medical Association. It summarized the evidence and recommended the key points for the clinical application of classic and novel hepatitis B virus related biomarkers in order to guide the standardized and reasonable clinical application for these biomarkers.
Humans ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Consensus ; Antiviral Agents/therapeutic use* ; Biomarkers ; Hepatitis B/drug therapy*

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Background: There is a dearth of data on Filipino patients with autoimmune hepatitis (AIH). We aimed to describe the demographic and clinical profiles of patients with AIH and to characterize clinical outcomes and treatment responses. Methods: A retrospective cohort study involving patients from two tertiary centers diagnosed with AIH from January 1, 2007, to December 31, 2019, was included. Disease remission was defined as the normalization of ALT levels, while failure was defined as an increase in ALT levels over baseline or clinical deterioration. Results: A total of 48 patients were identified between 2007 to 2019. The median age at presentation was 51 (27-79 yrs.). Liver cirrhosis was already present in 37.5% (27.1% decompensated) on diagnosis. Aside from a higher histologic activity index in females (p=0.047), there were no gender-specific differences. Disease remission was achieved in 41.9% of patients at 6 months, while only 9.3% failed. At the final disposition, remission rates had slightly increased to 58%, but failure rates had risen to 12%. Treatment responses at both 6 and 12 months and MELD and Child-Pugh class influenced treatment responses at final disposition. Median overall survival was 102 weeks and was influenced by the presence of liver dysfunction and 12 months and final treatment responses. Conclusion Autoimmune hepatitis remains an important cause of morbidity and mortality. The results of the study highlight the need for immunosuppressive therapy to induce early remission for a higher likelihood of subsequent biochemical remission to reduce the risk of liver-related mortality.
Autoimmune Hepatitis ; Liver Cirrhosis ; Steroids ; Azathioprine

Objective:b> This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods:b> Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ² Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results:b> Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion:b> In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Antiviral Agents/therapeutic use* ; DNA, Viral/therapeutic use* ; Retrospective Studies ; Mutation ; Drug Resistance, Viral/genetics* ; Lamivudine/therapeutic use*

Objective:b> To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods:b> A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results:b> A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions:b> Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.
Female ; Humans ; Child ; Glucocorticoids ; Retrospective Studies ; Hepatitis, Autoimmune/drug therapy* ; Alanine Transaminase ; Osteomyelitis/drug therapy*

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

This paper summarizes the incidence, modes of transmission, diagnosis, treatment and prevention of chronic hepatitis E.
Humans ; Hepatitis E/prevention & control* ; Hepatitis, Chronic/epidemiology* ; Incidence

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.
Humans ; Antiviral Agents/therapeutic use* ; Ribavirin/therapeutic use* ; Hepatitis, Chronic/drug therapy* ; Hepatitis E virus ; Liver Diseases/drug therapy* ; Liver Failure/drug therapy*