Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in controlling HBV infection; however, their function is impaired during chronic HBV infection, manifesting as a state of dysfunction. Recent studies have revealed that CD8⁺ T cell dysfunction in chronic HBV infection differs from the classical exhaustion observed in other viral infections or tumors. In 2024, several pivotal studies further elucidated novel mechanisms underlying CD8⁺ T cell dysfunction in chronic HBV infection and identified new therapeutic targets, including 4-1BB and transforming growth factor-beta (TGF-β). This review, while elucidating the dysfunction of CD8⁺ T cells in chronic HBV infection and its underlying mechanisms, focuses on summarizing the key findings from these latest studies and explores their translational value and clinical significance.
Humans ; Hepatitis B, Chronic/virology* ; CD8-Positive T-Lymphocytes/immunology* ; Hepatitis B virus/physiology* ; Animals ; Transforming Growth Factor beta/immunology*

OBJECTIVE: To study the results, re-donation situation and characteristics of single-reagent reactive blood donors who were put into the reentry strategy in Wuhan area, explore the rationality and effectiveness of the current reentry strategy, and provide data support for the improvement of the reentry process of blood donors. METHODS: From January 2020 to December 2023, blood donors who conform the reentry criteria and voluntarily applied for returning to Wuhan Blood Center were tested and the results were analyzed. According to the reentry strategy, serological testing and nucleic acid testing were carried out in parallel, serological testing was performed by ELISA with reagents from two different manufacturers, and the primary reactive samples were tested by double-well retest, and HBV/HCV/HIV nucleic acid detection was performed by RT-PCR with an individual donor test mode. Supplementary HBcAb testing was applied for HBV single reagent reactivity by chemiluminescence method. Supplementary TP-WB testing was applied for returning blood donors with repeated TP single reagent reactivity. If returning blood donors with HIV single reagent reactivity were repeated single reagent reactivity, the samples were sent to local CDC for confirmatory test. RESULTS: 7 098 blood donors were qualified for reentry, 716 donors voluntarily applied for reentry, 436 donors successfully reentry, 251 donors entered the next round, 29 donors could not reentry. The reentry rates for the past four years were 66.67%（42/63）, 54.73%（81/148）, 60.71%（136/224） and 62.99%（177/281）, respectively. Up to December 31, 2023, 275 donors donated blood again, and the donation rates for past four years were 76.19%（32/42）, 72.84%（59/81）, 61.76%（84/136） and 56.50%（100/177）, respectively. After donating blood, 31 donors were disqualified again by blood screening and subjected to permanent deferral. The results of returning to the team had statistical differences in reentry items, educational level, age, and marriage（P < 0.05）. CONCLUSION The current reentry strategy adopted by the blood donation and supply institution can effectively retain part of blood donors, reduce the negative emotions of blood donors and increase blood resources.
Humans ; Blood Donors ; China ; Hepatitis B ; Enzyme-Linked Immunosorbent Assay ; Hepatitis C ; Male

OBJECTIVE: To analyze the relationship between miR451a and occult hepatitis B virus infection (OBI) in voluntary blood donors, and to provide ideas for the identification of OBI. METHODS: A total of 125 003 blood samples were collected from voluntary blood donors in our center from January 2022 to June 2023, and OBI infection was detected by blood screening. At the same time, 40 HBsAg double reagent reactive samples (S/CO>3.0) were selected as the positive control group, and 40 healthy blood donors were selected as the negative control group (normal group). The plasma miR451a level was detected, and the serum indexes of total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST). The relationship between miR451a and OBI were analyzed. RESULTS: 54 out of 125 003 blood samples were diagnosed as OBI, and the OBI infection rate was 0.043% (54/125 003). Compared with the normal group, the relative expression of plasma miR451a in the OBI group and the positive control group was down-regulated (P < 0.05), but there was no significant difference in the relative expression of plasma miR451a between the OBI group and the positive control group (P >0.05). The HBV DNA load, TBil, ALT and AST levels in the positive control group were higher than those in the OBI group and the normal group (P < 0.05). There was no significant difference in plasma TBil, ALT and AST levels between OBI group and normal group (P >0.05). Logistic regression analysis and receiver operating curve (ROC) showed that plasma miR451a could distinguish OBI group from healthy group, and the area under the curve (AUC) was 0.904 (95%CI : 0.829-0.978). However, plasma miR451a was difficult to distinguish between OBI and HBsAg responders. CONCLUSION Plasma miR451a can be used as a potential biomarker for HBV infection, and can be used to identify OBI in HBsAg non-reactive blood donors.
Humans ; MicroRNAs/blood* ; Blood Donors ; Hepatitis B/blood* ; Hepatitis B virus ; Alanine Transaminase/blood* ; Aspartate Aminotransferases/blood* ; Female ; Male ; Adult ; Hepatitis B Surface Antigens/blood*

OBJECTIVE: To investigate the pattern of hepatitis B virus (HBV) infection and the prevalence of hepatitis D virus (HDV) infection among voluntary blood donors who tested reactive for HBV in Wuhan, and to provide data support for the prevention and treatment of HBV and HDV infections. METHODS: Electrochemiluminescence (ECL) method was used to detect hepatitis B serological markers in the samples with HBsAg and/or HBV DNA reactivity, and the HBV infection in different groups was statistically analyzed. The HDV IgM and IgG antibodies were screened by ELISA, and the prevalence of HDV infection in the retained samples was analyzed. RESULTS: In 351 ELISA and/or nucleic acid test (NAT) reactive samples, the serological tests for hepatitis B revealed that 4 cases (1.1%) were positive for HBsAg, HBeAg, and anti-HBc, 182 cases (51.9%) were positive for HBsAg, anti-HBe, and anti-HBc, and 55 cases (15.7%) were negative for HBsAg but positive for anti-HBc. Among them, the HBsAg ELISA dual reagent reactive group (HBsAg R&R group) and the HBsAg ELISA single reagent reactive/HBV DNA reactive group (HBsAg R&NR/HBV DNA R group) had the highest rates of HBsAg(+), anti-HBe(+), and anti-HBc(+), accounting for more than 90% and 65%, respectively, followed by low activity of HBV acute infection or chronic carriers, accounting for about 5% and 20%, respectively. In the HBsAg R&NR/HBV DNA NR group, the combined proportion of individuals with anti-HBs single positive and all hepatitis B serological markers negative accounted for 78%, and those who were HBsAg negative but anti-HBc positive accounted for approximately 20%. In the HBsAg NR&NR/HBV DNA R group, there was nearly 9% of HBsAg(+), anti-HBe(+), and anti-HBc(+), the remaining were all HBsAg negative but anti-HBc positive, with a 100% anti-HBc positivity rate in this group. No HDV IgM or IgG antibodies were detected in the retained samples. CONCLUSION Blood donors with HBV-reactive results in blood screening exhibit multiple patterns of infection indicators. The prevalence rate of HDV infection among blood donors in Wuhan is extremely low. However, the risk of asymptomatic occult hepatitis B infection (OBI) blood donors being co-infected with HDV should not be overlooked in areas with high prevalence of HBV.
Humans ; Blood Donors ; Hepatitis B/blood* ; China/epidemiology* ; Adult ; Male ; Female ; Hepatitis D/epidemiology* ; Middle Aged ; Hepatitis B virus/immunology* ; Hepatitis B Antibodies/blood* ; Young Adult ; DNA, Viral/blood* ; Hepatitis B Surface Antigens/blood* ; Prevalence ; Adolescent

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

OBJECTIVES: To evaluate whether adding Fuzheng Jiedu Xiaoji (FZJDXJ) therapy improves survival in advanced hepatitis B virus-related HCC (HBV-HCC) patients. METHODS: This prospective, randomized controlled study was performed at a major academic medical center in Beijing, China from October 2020 to October 2022. Eligible patients with advanced HBV-HCC were randomly divided equally (1:1) to receive either the combination of FZJDXJ and conventional Western medical therapy (63 cases, FZJDXJ group) or solely Western medicine (66 cases, control group). The study endpoints consisted of overall survival (OS) as the primary outcome, with progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs) as secondary measures. RESULTS: The median OS was significantly prolonged in the FZJDXJ group at 8.9 months (95% CI: 6.0-11.9) vs. 4.4 months (95% CI: 3.2-7.3) in the control group (P<0.05). The hazard ratio for mortality in the FZJDXJ group was 0.59 (95% CI: 0.40-0.89), suggesting a 41% lower risk of death compared to the control group. The results revealed that patients receiving FZJDXJ therapy achieved a PFS of 5.1 months (95% CI: 4.1 to 7.2 months), compared to only 2.9 months (95% CI: 2.0 to 4.6 months) in the control group (P<0.05). Additionally, DCR was significantly elevated in the FZJDXJ group (20.6%) compared to the control group (10.6%, P<0.05). Subgroup analysis demonstrated that FZJDXJ significantly improved OS in patients with alpha-fetoprotein levels <400 ng/mL, age <60 years, Barcelona Clinic Liver Cancer (BCLC) stage C, and compensated liver function (Child-Pugh A and B, P<0.05). Multivariate analysis revealed that FZJDXJ therapy acted as an independent factor protecting against mortality within 1 year. Gastrointestinal symptoms are rare side effects, and no fatalities associated with the treatment were reported. CONCLUSION This randomized controlled trial demonstrated that FZJDXJ combined Western conventional therapy significantly improves OS and PFS in patients with advanced HBV-HCC. (registration No. ChiCTR2000033941).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/virology* ; Carcinoma, Hepatocellular/virology* ; Treatment Outcome ; Hepatitis B virus ; Adult ; Aged ; Hepatitis B/drug therapy*

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

OBJECTIVES: To investigate the impact of hepatitis B virus (HBV) infection on oral microbiota and metabolites in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and the underlying mechanisms. METHODS: This prospective study was conducted in 47 MAFLD patients complicated with chronic hepatitis B (CHB) and 48 MAFLD patients without CHB enrolled from November, 2023 to January, 2024. Fasting tongue coating samples were collected from the patients for analyzing microbial community structures and metabolites using high-throughput 16S rDNA sequencing and non-targeted metabolomics techniques, and their associations with clinical indicators and biological pathways were explored using correlation analysis and functional annotation. RESULTS: The levels of fasting blood glucose, total cholesterol (TC), gamma-glutamyl transferase (GGT), and severity of fatty liver were all significantly lower in MAFLD+CHB group than in MAFLD group. Microbiota analysis showed that the abundances of Patescibacteria (at the phylum level), Hydrogenophaga, and Absconditabacteriales (at the genus level) were significantly increased, while the abundance of Megasphaera was decreased in MAFLD+CHB group. The differential microbiota were significantly correlated with TC, GGT and low-density lipoprotein (r=-0.68‒0.75). Metabolomics analysis revealed that 469 metabolites (including lipids and amino acids) were upregulated and 2306 (including organic oxygen-containing compounds and phenylpropanoids) were downregulated in MAFLD+CHB group, for which KEGG enrichment analysis suggested abnormal activation of the linoleic acid metabolism and glycerophospholipid metabolism pathways. Correlation analysis between microbiota and metabolites indicated that Patescibacteria and Megasphaera, which were positively correlated with lipid metabolites and negatively with fatty acid metabolites, respectively, jointly affected glycolipid metabolism and oxidative stress pathways. CONCLUSIONS Compared to patients with MAFLD alone, MAFLD patients with concurrent chronic HBV infection showed lower levels in some lipid metabolism indicators and the degree of hepatic steatosis, accompanied by alterations in oral microbiota structure and metabolic profiles. The precise mechanisms involved require further investigation to be fully elucidated.
Humans ; Lipid Metabolism ; Prospective Studies ; Microbiota ; Hepatitis B, Chronic/microbiology* ; Male ; Female ; Adult ; Fatty Liver/microbiology* ; Middle Aged ; Mouth/microbiology* ; Metabolomics

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.