Response In Chronic Hepatitis Research Articles

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide.

An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. Patients were treated with TAF monotherapy for 96weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1logIU/mL from baseline) were evaluated. The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7logIU/mL. The median change in HBcrAg from baseline was -1.1logIU/mL at 96weeks after treatment. The HBcrAg response rate at 96weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96weeks of treatment (p=4.53×10-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Clinical implications of hepatitis B virus core antigen-mediated immunopathologic T cell responses in chronic hepatitis B.

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.

A genetic variant of CXCR4 predicts pegylated interferon-alpha treatment response in HBeAg-positive chronic hepatitis B patients.

Chemokine receptor 4 (CXCR4) plays a vital role in immunoregulation during hepatitis B virus (HBV) infection. This study aimed to screen single-nucleotide polymorphisms (SNPs) of CXCR4 for predicting pegylated interferon-alpha (PegIFNα) therapy response in chronic hepatitis B (CHB) patients. This retrospective cohort study enrolled a total of 945 CHB patients in two cohorts (Cohort 1, n = 238; Cohort 2, n = 707), and all the patients were hepatitis B e antigen (HBeAg)-positive and treated with PegIFNα for 48 weeks and followed up for 24 weeks. Twenty-two tag SNPs were selected in CXCR4 and its flanking region. A polygenic score (PGS) was utilized to evaluate the cumulative effect of multiple SNPs. The relationships between CXCR4 SNPs and PGS and PegIFNα treatment response were explored in the two cohorts. Among the 22 candidate SNPs of CXCR4, rs28367495 (T > C) was significantly linked to PegIFNα treatment response in both cohorts. In patients with more number of rs28367495 C allele, a higher rate of combined response (CR, defined as HBeAg seroconversion and HBV DNA level < 3.3 log10 IU/mL; P = 1.51 × 10-4), a lower mean hepatitis B surface antigen (HBsAg) level (P = 4.76 × 10-4), and a higher mean HBsAg decline (P = 3.88 × 10-4) at Week 72 were achieved. Moreover, a PGS integrating CXCR4_rs28367495 and five previously reported SNPs was strongly correlated with CR (P = 1.26 × 10-13), HBsAg level (P = 4.90 × 10-4), and HBsAg decline (P = 0.005) in all the patients of the two cohorts. CXCR4_rs28367495 is a promising indicator for predicting the responsiveness to PegIFNα treatment for HBeAg-positive CHB patients. The new PGS may further improve the prediction performance.

A Cytokine That Is Involved in Immune Responses in Chronic Hepatitis B Virus Patients

Abstract Background: The present research examines the part interleukin-17 (IL-17) plays in the progression of liver disease in people infected with the long-term hepatitis B virus. A proinflammatory cytokine called IL-17, linked to a number of autoimmune disorders, was examined in serum samples taken from different participant groups. Objective: The aim of this study is to examine the levels of IL-17 in various participant groups and understand any possible influence on the development and course of liver fibrosis. Materials and Methods: There were four groups in the study: asymptomatic HBsAg carriers (n = 42), chronic hepatitis B (CHB, n = 57), liver cirrhosis (LC, n = 59), and the normal control group (n = 80). an Enzyme-Linked was used to measure the amounts of IL-17, while reverse transcription polymerase chain reaction was used to find IL-17 mRNA in peripheral blood mononuclear cells (PBMC). Results: Liver disorders such as cirrhosis and CHB are associated with elevated levels of IL-17. Both the subjects’ serum and PBMCs showed these elevated IL-17 levels, demonstrating a strong correlation with inflammation. These findings highlight the significant function of IL-17 in the possible management or treatment of a variety of liver-related conditions. Conclusion: The investigation comes to the conclusion that IL-17 levels increase as liver disease severity increases, suggesting that it is involved in the development of fibrosis and the progression of the disease. Gaining insight into the function of IL-17 may help develop more effective therapies for CHB and LC patients. It is crucial to conduct further research in this area to develop tailored therapeutics.

Occult hepatitis B infection and clinical implications; a systematic review

Occult hepatitis B infection (OBI) is the presence of replication-competent DNA of the hepatitis B virus in the blood or liver of individuals who display a negative test for hepatitis B surface antigen. There are many clinical implications of OBI, including blood product transfusion, the occurrence of cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation. OBI is associated with the development of hepatocellular carcinoma and might influence the progression of the disease, and the response of chronic hepatitis C to the treatment. Thus, this review was conducted to assess the clinical implications of OBI by reviewing the previous studies conducted on this subject. Electronic databases, including PubMed, BioMed Central, Scopus, Elsevier, Springer, Cochrane Library, Web of Science, and Science Direct, were revised for articles published between 2013 and 2023. A total of 2,880 articles were obtained, and only ten articles were found eligible and were included in the final analysis. There was heterogeneity in findings between the included studies; however, it was concluded that OBI could cause the progression to HCC and cause deterioration in HCV patients based on the presence of additive risk factors.

Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B.

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir. Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson's or Spearman's correlation analysis. Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r 2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014). Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.

Association of HBsAg levels with differential gene expression in NK, CD8 T, and memory B cells in treated patients with chronic HBV

HBsAg secretion may impact immune responses to chronic HBV infection. Thus, therapeutic approaches to suppress HBsAg production are being investigated. Our study aims to examine the immunomodulatory effects of high and low levels of circulating HBsAg and thereby improve our understanding of anti-HBV immunity. An optimized 10x Genomics single-cell RNA sequencing workflow was applied to blood samples and liver fine-needle aspirates from 18 patients undergoing tenofovir/entecavir (NUC) treatment for chronic HBV infection. They were categorized based on their HBsAg levels: high (920-12,447 IU/ml) or low (1-100 IU/ml). Cluster frequencies, differential gene expression, and phenotypes were analyzed. In the blood of HBV-infected patients on NUC, the proportion of KLRC2+ "adaptive" natural killer (NK) cells was significantly lower in the HBsAg-high group and, remarkably, both KLRC2+ NK and KLRG1+ CD8 T cells display enrichment of lymphocyte activation-associated gene sets in the HBsAg-low group. High levels of HBsAg were associated with mild immune activation in the liver. However, no suppression of liver-resident CXCR6+ NCAM1+ NK or CXCR6+ CD69+ CD8 T cells was detected, while memory B cells showed signs of activation in both the blood and liver. Among NUC-treated patients, we observed a minimal impact of HBsAg on leukocyte populations in the blood and liver. However, for the first time, we found that HBsAg has distinct effects, restricted to NK-, CD8 T-, and memory B-cell subsets, in the blood and liver. Our findings are highly relevant for current clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. This study provides unique insight into the impact of HBsAg on gene expression levels of immune cell subsets in the blood and liver, particularly in the context of NUC-treated chronic HBV infection. It holds significant relevance for current and future clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. Our findings raise questions about the effectiveness of such treatment strategies and challenge the previously hypothesized immunomodulatory effects of HBsAg on immune responses against HBV.

Switching from entecavir to tenofovir alafenamide for maintaining complete virological response in chronic hepatitis B.

Hepatocellular carcinoma development can be decreased by achieving and maintaining complete virological response (CVR) in chronic hepatitis B. However, it is unclear whether switching from entecavir (ETV) to tenofovir alafenamide (TAF) could achieve and maintain CVR in patients with low-level viremia (LLV; HBV DNA ≤ 3.3 log IU/mL) or occasional detectable HBV DNA during ETV treatment. Therefore, we aimed to examine whether the switching from ETV to TAF is effective in achieving CVR in patients with LLV or occasional detectable HBV DNA. This study comprised 45 patients who switched from ETV to TAF. All patients received ETV and TAF for >2 years, and the HBV DNA levels were measured every 3 months. Maintaining undetectable HBV DNA during 2-year period is defined as CVR. The primary endpoint is the CVR rate during ETV and TAF treatment. The CVR rate for each of the 2 years of ETV and TAF therapy was 33.3% (15/45) and 68.9% (31/45, P < 0.01), respectively, and the CVR rate increased by switching from ETV to TAF. In patients with occasional detectable HBV DNA during ETV treatment (22 patients), 15 achieved CVR and 7 maintained occasional detectable HBV DNA. In patients with LLV during ETV treatment (eight patients), three achieved CVR and five had occasional detectable HBV DNA. Switching from ETV to TAF increases the CVR rate in patients with LLV or occasional detectable HBV DNA and could be an alternative treatment option.

Dysregulation of T Cell Differentiation and the IL17A(+)Foxp3(+)Treg Subset in Chronic Hepatitis B Patients with Hepatitis Flare.

The regulatory T (Treg) and T helper 17 (Th17) cells modulate the immune response in chronic hepatitis B virus (HBV) infection by promoting immune tolerance and restricting liver damage or stimulating inflammatory response and rendering hepatocyte injury. These cells act through signaling transcription factors and secreting cytokines. We aimed to observe the percentages of Treg, Th17 cells, and their messenger RNA (mRNA) level of forkhead box protein 3 (Foxp3) and retinoid orphan receptor γt (RORγt) in the chronic hepatitis B (CHB)-infected group and CHB patients with hepatitis flare (HF). We recruited 103 participants, including 88 CHB-infected cases and 15 healthy controls (HCs) in Ho Chi Minh City. CHB cases were enrolled into two groups: HBeAg+ CHB infection (e+CHBI; n = 42) and HF (including 20 mild HF and 26 severe HF [sHF]). The Foxp3(+)Treg and Th17 cells were measured by flow cytometry. The mRNA levels of Foxp3 and RORγt were analyzed by real-time polymerase chain reaction. The percentages of Foxp3(+)Treg, of Th17, and the Foxp3(+)Treg/Th17 ratio were significantly higher in the sHF compared to the e+CHBI group. The sHF and e+CHBI groups had significantly higher mRNA levels of Foxp3 and RORγt compared to the HC group. Furthermore, a special subset, interleukin 17A(+)Foxp3(+)Treg cells, were observed with a significantly higher percentage in the sHF compared to the e+CHBI group. This finding revealed the contributions of this new subset on the severe flare cases. Our results explained the diversity of T cells and their subsets in the immune response in CHB. This subset should be further investigated as a specific tool in HBV immune response.

Evaluation of Direct-acting Antiviral Agents and Clinical Responses in Chronic Hepatitis C Patients

Evaluation of Direct-acting Antiviral Agents and Clinical Responses in Chronic Hepatitis C Patients

Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner

ObjectivesDissecting the underlying mechanism of T cells remodeling mediated by interferon α (IFN-α) is indispensable for achieving an optimum therapeutic response in chronic hepatitis B (CHB) patients. However, little is known about B cells in this process. This study aims to elucidate the roles of B cells in IFN-α-mediated anti-hepatitis B virus (HBV) cellular immunity. MethodThe effects of B cells on IFN-α-mediated T cell response were investigated in B cell-deficient mouse model with HBV and IFN-α plasmid hydrodynamic injection. Single-cell RNA sequencing was performed to dissect the crosstalk among B cell and T cell subsets and the underlying molecule and pathway signatures on longitudinal blood samples from IFN-α-treated CHB patients. ResultsB cell depletion impaired the functional T cell subsets, including HBV-specific CD8+ T cells, and engendered a delayed HBV clearance. IFN-α treatment boosted the response of HBV-specific CD8+ T cells, whereas such effects disappeared in B cell-deficient mice. The underlying mechanisms were associated with IFN-α-reinforced connections of B cells toward T cells as mediated by the antigen presentation and costimulatory functions in B cells. ConclusionIFN-α orchestrates protective HBV-specific cellular immunity in a B cell-dependent manner.

The Prognostic Value of Serum HBV-RNA during Hepatitis B Virus Infection is Related to Acute-on-Chronic Liver Failure.

Background Serum HBV-RNA levels can predict antiviral response in chronic hepatitis B (CHB) patients; however, its role in HBV-related ACLF (HBV-ACLF) remains unclear. Here, we determined its implications for HBV-ACLF. Methods Baseline serum HBV-RNA levels were retrospectively detected in HBV-ACLF and CHB patients. The association of serum HBV-RNA level with clinical outcomes was evaluated by performing multiple logistic regression. A nomogram was developed to formulate an algorithm incorporating serum HBV-RNA for predicting the survival of HBV-ACLF patients. After being discharged from the hospital, the HBV-ACLF patients were followed up for 36 weeks. Results In this study, 82 HBV-ACLF patients and 33 CHB patients were included. Serum HBV-RNA levels were significantly higher in CHB patients than in HBV-ACLF patients (4.15 ± 2.63 log10 copies/mL VS 5.37 ± 2.02 log10 copies/mL) (P < 0.05). Among the HBV-ACLF cases, patients with poor outcomes had lower serum HBV-RNA levels, but the difference was not significant. The area under the receiver operating characteristic curve of the serum HBV-RNA inclusive model was 0.745, superior to 0.66 from MELD scores (P < 0.05). During the follow-up for four weeks, the serum HBV-RNA levels, especially in the survival group, were found to be lower than the baseline levels. Conclusions Serum HBV-RNA levels were associated with disease severity and might predict the long-term clinical outcome of HBV-ACLF patients.

Does Hepatic Steatosis Influence the Virological Response with Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir Disoproxil Fumarate?

The effect of hepatic steatosis on the response to antiviral therapy administered in chronic hepatitis B patients is yet to be clarified. In this study, our aim was to determine the effect of hepatic steatosis on the virological response in chronic hepatitis B patients who were treated with entecavir or tenofovir disoproxil fumarate. This retrospective cohort study was performed using the data of liver biopsy-proven chronic hepatitis B patients with or without hepatic steatosis, who received entecavir or tenofovir disoproxil fumarate treatment between 2012 and 2017. The undetectable serum hepatitis B virus deoxyribonucleic acid level under treatment was defined as the complete virological response. The predictors of virological response were determined, and it was checked whether the virological response was affected by hepatic steatosis in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment. A total of 324 chronic hepatitis B patients, of which 203 (63%) were males, were included in the study. The median age of the patients was 42 years (range: 35-51 years). Hepatic steatosis was observed in 25% of the patients, and steatohepatitis in 4%. The median time to complete virological response was found to be 6 months (range: 3-9 months). In the full analysis model, the log hepatitis B virus deoxyribonucleic acid was determined as the factor most associated with virological response (P < .001). No statistically signifi- cant relationship was detected between hepatic steatosis and virological response (P = .409). Concomitant hepatic steatosis has no significant impact on the virological response in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment.

Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C.

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non‐HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non‐HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct‐acting antiviral (DAA) treatment were analyzed. The cumulative post‐SVR incidence of non‐HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non‐HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac‐2‐binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post‐SVR incidence of non‐HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post‐SVR incidence of non‐HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post‐SVR incidence of non‐HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P&lt;0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (?400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.

High levels of soluble programmed death-1 are associated with virological response in chronic hepatitis B patients after antiviral treatment

BackgroundSoluble programmed cell death protein-1 (sPD-1) plays an important role in chronic hepatitis B virus (HBV) infection by counteracting the inhibitory effect of programmed death ligand-1 (PD-L1) on immune cells. Here, we investigated the ability of sPD-1 to predict the virological response (VR) in chronic hepatitis B (CHB) patients undergoing Nucleos(t)ide analogue (NA) therapy. MethodsCHB patients [hepatitis B surface antigen (HBsAg) positive ≥6 months] who initiated NA therapy in March 2007 at Peking University First Hospital (China) were enrolled in this study. Eighty-nine CHB patients were followed-up every 12 weeks for 96 weeks. ResultsSerum sPD-1 levels at baseline were negatively correlated with hepatitis B surface antigen (HBsAg) and HBV DNA. Immune-active CHB patients exhibited higher serum sPD-1 levels at baseline. Patients with VR during the antiviral treatment exhibited higher sPD-1 levels and lower HBsAg levels at baseline. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of sPD-1 and HBsAg for VR in patients who received first-line therapy (entecavir, ETV). The area under ROC (AUROC) values of sPD-1 and HBsAg at baseline were 0.850 (95%CI:0.729–0.971, P = 0.0005) and 0.785 (95%CI: 0.642–0.929, P = 0.005), respectively, and the optimal cut-off values were 459.46 pg/mL and 14,710 IU/mL, respectively. The combination of sPD-1 and HBsAg exhibited a higher AUROC value (0.870,95% CI: 0.748–0.983, P = 0.001) than did sPD-1 or HBsAg alone. In patients administered second-line therapy (lamivudine, LAM/adefovir divipoxil, ADV), baseline sPD-1 levels above 677.2 pg/mL were significantly associated with higher incidence of VR after 96 weeks of antiviral therapy. It is 7.956 times the level of ≤677.2 pg/mL. ConclusionsBy combining sPD-1 and HBsAg, we obtained a biomarker significantly associated with VR in CHB patients. The sPD-1 levels could be used to screen out patients with poor prognosis of antiviral therapy.

From the Editor’s Desk...

From the Editor’s Desk...

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Interleukin-33 Reinvigorates Antiviral Function of Viral-Specific CD8+ T Cells in Chronic Hepatitis B Virus Infection.

Restoration of exhausted hepatitis B virus (HBV)-specific CD8+ T cells is one of the important strategies for inhibition of viral replication. The role of interleukin (IL)-33 to recovery of CD8+ T cell activity is not fully elucidated. We investigated the effect of IL-33 on viral-specific CD8+ T cell responses in chronic hepatitis B (CHB) patients in vitro by both phenotypic and functional analysis. Plasma IL-33 was downregulated in CHB patients, while effective antiviral therapy rescued IL-33 expression. There was no significant difference of IL-33 receptor mRNA relative level in CD8+ T cells between CHB patients and controls. IL-33 induced the proliferation of HBV-specific CD8+ T cells, and reduced programmed death-1 expression on HBV-specific CD8+ T cells. IL-33 promoted the direct cytolytic activity of CD8+ T cells against HepG2.2.15 cells through boosting perforin and granzyme B production. Furthermore, IL-33 administration increased HBV-specific CD8+ T cell-mediated HBV replication and HBV antigen secretion mainly via enhancement of interferon-γ and tumor necrosis factor-α. IL-33 reinvigorated antiviral activity of HBV-specific CD8+ T cells, revealing that IL-33 might contribute to viral clearance in persistent HBV infection.