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*

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

Objective:b> To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods:b> Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results:b> The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P＜0.01], 0.949 [95% CI: 0.916-0.982, P＜0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P＜0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P＜0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P＜0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion:b> Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.
Disease Progression ; Gastrointestinal Hemorrhage/etiology* ; Hepatitis B/complications* ; Hepatitis B virus ; Hepatitis B, Chronic/diagnosis* ; Humans ; Liver Cirrhosis/virology* ; Peritonitis/complications* ; von Willebrand Factor/analysis*

OBJECTIVE: To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels. METHODS: We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)]. RESULTS: In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05). CONCLUSIONS In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.
Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; drug therapy ; enzymology ; immunology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Viral Load ; drug effects

OBJECTIVE: To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS: A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
Carcinoma, Hepatocellular ; blood ; diagnosis ; virology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; DNA, Viral ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Liver Cirrhosis ; virology ; Liver Neoplasms ; blood ; diagnosis ; virology ; Mass Spectrometry ; Metabolome ; Metabolomics ; ROC Curve

Based on the progression of clinical and basic research in hepatitis B virus (HBV), we updated the previous HBV guidelines from 2015. The guidelines included the prevention, diagnosis, and antiviral therapy of chronic hepatitis B, which accelerates ro achieve the goal of "the elimination of viral hepatitis as a public health threat by 2030" proposed by the World Health Organization.
Antiviral Agents/therapeutic use* ; Hepatitis B virus/isolation & purification* ; Hepatitis B, Chronic/virology* ; Humans ; Practice Guidelines as Topic ; Public Health ; World Health Organization

To investigate whether transcription of hepatitis B virus (HBV) gene occurs in human sperm, total RNA was extracted from sperm of patients with chronic HBV infection (test-1), from donor sperm transfected with a plasmid containing the full-length HBV genome (test-2), and from nontransfected donor sperm (control), used as the template for reverse transcription-polymerase chain reaction (RT-PCR). Positive bands for HBV DNA were observed in the test groups but not in the control. Next, to identify the role of host genes in regulating viral gene transcription in sperm, total RNA was extracted from 2-cell embryos derived from hamster oocytes fertilized in vitro by HBV-transfected (test) or nontransfected (control) human sperm and successively subjected to SMART-PCR, suppression subtractive hybridization, T/A cloning, bacterial amplification, microarray hybridization, sequencing and the Basic Local Alignment Search Tool (BLAST) search to isolate differentially expressed genes. Twenty-nine sequences showing significant identity to five human gene families were identified, with chorionic somatomammotropin hormone 2 (CSH2), eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), pterin-4 alpha-carbinolamine dehydratase 2 (PCBD2), pregnancy-specific beta-1-glycoprotein 4 (PSG4) and titin (TTN) selected to represent target genes. Using real-time quantitative RT-PCR (qRT-PCR), when CSH2 and PCBD2 (or EIF4G2, PSG4 and TTN) were silenced by RNA interference, transcriptional levels of HBV s and x genes significantly decreased (or increased) (P < 0.05). Silencing of a control gene in sperm did not significantly change transcription of HBV s and x genes (P > 0.05). This study provides the first experimental evidence that transcription of HBV genes occurs in human sperm and is regulated by host genes.
Animals ; Connectin/genetics* ; Cricetinae ; Eukaryotic Initiation Factor-4G/genetics* ; Gene Expression Regulation/genetics* ; Gene Silencing ; Growth Hormone/genetics* ; Hepatitis B Surface Antigens/genetics* ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/virology* ; Humans ; Hydro-Lyases/metabolism* ; Male ; Pregnancy-Specific beta 1-Glycoproteins/genetics* ; RNA, Viral/analysis* ; Spermatozoa/virology* ; Trans-Activators/genetics* ; Transcription, Genetic ; Transfection ; Viral Regulatory and Accessory Proteins

<b>Objective:b> To investigate the effects of hepatitis B virus (HBV) genotype and mutations on the development of hepatocellular carcinoma (HCC) and to establish a new qualified HCC risk scores. <b>Methods:b> A cohort study enrolling patients with chronic HBV infection was conducted. HBV genotypes were identified by nested multiplex PCR. HBV mutations in the basic core promoter region and PreS region were sequenced after PCR amplification. Scores on risk factors were set based on nomogram. <b>Results:b> Totally, 1 525 patients were followed-up in this research. A total of 1 110 patients infected with genotype C were followed-up for 8.52 (Q(R): 5.36-11.68) years on average, of whom the incidence of HCC was 11.93/1 000 person-years. In genotype C HBV infected patients, male gender, aged 40 years and over, and four DNA mutations (T1674CG, A1762T/G1764A, A3120T, and A2962G) can increase the risk of HCC (P<0.05); interferon therapy can reduce the risk of HCC (P<0.05). A new HCC predicting model was established according to the results. After validation, the predicted disease-free survival rate was consistent with the real one. <b>Conclusions:b> Hepatitis B virus genotypes and mutations were closely associated with HCC. The new risk scoring system can well predict HCC occurrence in genotype C HBV infected patients.
Adult ; Aged ; Carcinoma, Hepatocellular/virology* ; China/epidemiology* ; Cohort Studies ; DNA, Viral/genetics* ; Female ; Genotype ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/complications* ; Humans ; Liver Neoplasms/virology* ; Male ; Middle Aged ; Mutation ; Predictive Value of Tests ; Risk Factors ; Sensitivity and Specificity

<b>Objective:b> To explore the SNP effects of patatin-like phospholipase domain which containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) gene, environmental effects of smoking, alcohol drinking and interaction between gene-gene, gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). <b>Methods:b> We collected anticoagulant peripheral blood from patients of HBV-HCC, chronic hepatitis B (CHB), liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926, using the flight mass spectrometry method. The optimal assignment value of gene polymorphisms was defined by using the online SNP stats. Hardy-Weinberg (H-W) balance was tested for SNP. Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method. The gene-gene, gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods. <b>Results:b> The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (χ(2)=11.980, P<0.005). Two loci frequency distributions in the other groups were all in accordandce with the H-W balance. After adjusting for influences on age and sex and comparing to the healthy group, the rs58542926 mutation appeared as OR=1.659, 95%CI: 1.026-2.684, P=0.039, in the HBV-HCC group. When comparing to CHB group, the HBV-HCC group presented that drinking as OR=1.680, 95%CI: 1.121-2.519, P=0.012. When comparing to the LC group, the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively, in the HBV-HCC group. When comparing to the CHB+LC group, interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885, P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965, P=0.024). As for drinking and mutation of rs738409, the multiplication model of logistic regression showed no statistically significant differences. Interaction between smoking and drinking appeared as OR=1.756 (P<0.001) in the logistics regression multiplication model. <b>Conclusions:b> Factors as mutation of TM6SF2, smoking and drinking all appeared as risk factors for HBV-HCC. Mutations of both PNPLA3 and TM6SF2, together with smoking and drinking all served as risk factors for HBV-HCC. However, the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
Alcohol Drinking/adverse effects* ; Carcinoma, Hepatocellular/virology* ; Case-Control Studies ; Epistasis, Genetic ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genotype ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Lipase/genetics* ; Liver Cirrhosis, Alcoholic/complications* ; Liver Neoplasms/virology* ; Membrane Proteins/genetics* ; Polymorphism, Single Nucleotide ; Smoking/adverse effects*

The mother-to-child transmission(MTCT) of hepatitis B virus (HBV) is the dominant cause of chronic HBV infection. In order to achieve the goal of "zero" MTCT before pregnancy, during pregnancy, and after pregnancy; standardized management for hepatitis HBV infection in women of childbearing age should be regulated. The content of this consensus includes: screening and treatment of HBV in pregnant women and women of childbearing age, treatment of hepatitis B during pregnancy, preventive measures and evaluation of combined immunization of hepatitis B immunoglobulin and hepatitis B vaccine in newborns, anti-viral therapy for all pregnant women with a high HBV DNA level and post-partum period related management. In addition, 16 recommendations were formed for clinicians to standardize the clinical management of HBV infection in women of child-bearing age.
Child ; Consensus ; Female ; Hepatitis B/virology* ; Hepatitis B Vaccines/administration & dosage* ; Hepatitis B virus ; Hepatitis B, Chronic/prevention & control* ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/prevention & control* ; Pregnancy ; Pregnancy Complications, Infectious/prevention & control*