Objective:To investigate and explore the expressional condition and therapeutic role of PD-1 and CD161 in the peripheral blood of patients treated with PEG-IFN-α for chronic hepatitis B (CHB), and their correlation with the degree of decrease in hepatitis B surface antigen (HBsAg).Methods:A retrospective cohort study was conducted. CHB patients who visited the Second Affiliated Hospital of Xi'an Jiaotong University from July 2022 to December 2023 and healthy controls during the same period were included. Peripheral blood samples were collected from the IFN treatment group (31 cases), the non-IFN treatment group (30 cases), and the healthy control group (30 cases). Flow cytometry was used to detect the CD8, + PD-1, + CD161 + T lymphocytes and their subpopulations among the three groups. The proportions of cellular subpopulations were compared to analyze intergroup differences using Kruskal-Wallis and Mann-Whitney U tests. The patients in the IFN treatment group were divided into two subgroups, high-and low-level, according to the median levels of PD-1 + lymphocytes, CD8 +PD-1 +T cells, and CD161 + lymphocytes. The magnitude of HBsAg decline was compared between the two groups. Results:The proportions of PD-1 + lymphocytes and CD8 +PD-1 +T cells in the IFN treatment group were significantly higher than those in the healthy control group and the non-IFN treatment group ( P<0.001). Moreover, the proportions of PD-1 + lymphocytes [IFN treatment group 48 weeks: 24.3 (23.7, 28.0)%, non-IFN treatment group: 12.7 (10.0, 18.5)%, P<0.01] and CD8 +PD-1 +T cells [IFN treatment group 48 weeks: 29.29 (26.73, 32.98)%, non-IFN treatment group: 17.69 (9.62, 20.68)%, P<0.05] were higher in the IFN treatment group than those in the non-IFN treatment group at 48 weeks. The proportion of CD8 +CD161 +T cells was significantly lower in patients treated with IFN than in the non-IFN treatment group ( P<0.05) at 24 and 48 weeks, with no statistically significant difference with the healthy control group ( P>0.05). In the IFN treatment group, patients with high levels of PD-1 + and CD8 + PD1 lymphocytes had a significantly lower HBsAg decline compared to low-level patients, whereas no significant correlation was found between CD161 levels and HBsAg decline [PD-1 + lymphocytes: 0.15 (0.02, 0.18) log 10 IU/mL vs. 0.32 (0.13, 0.42) log 10 IU/mL, P<0.01; CD8 +PD-1 +T cells: 0.16 (0.03, 0.17) log 10 IU/mL vs. 0.34 (0.13, 0.44) log 10 IU/mL, P<0.05]. Conclusion:The proportions of CD8 +PD-1 +T cells and CD8 +CD161 +T cells were significantly regulated by PEG-IFN-α therapy in the peripheral blood of patients with CHB, revealing the important role of T cell immune activation status during antiviral treatment. The gradual decline of HBsAg is closely related to the high expression of PD-1, suggesting that PD-1 may be negatively regulated during the process of T cell exhaustion and immunological evasion.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective:To investigate and explore the expressional condition and therapeutic role of PD-1 and CD161 in the peripheral blood of patients treated with PEG-IFN-α for chronic hepatitis B (CHB), and their correlation with the degree of decrease in hepatitis B surface antigen (HBsAg).Methods:A retrospective cohort study was conducted. CHB patients who visited the Second Affiliated Hospital of Xi'an Jiaotong University from July 2022 to December 2023 and healthy controls during the same period were included. Peripheral blood samples were collected from the IFN treatment group (31 cases), the non-IFN treatment group (30 cases), and the healthy control group (30 cases). Flow cytometry was used to detect the CD8, + PD-1, + CD161 + T lymphocytes and their subpopulations among the three groups. The proportions of cellular subpopulations were compared to analyze intergroup differences using Kruskal-Wallis and Mann-Whitney U tests. The patients in the IFN treatment group were divided into two subgroups, high-and low-level, according to the median levels of PD-1 + lymphocytes, CD8 +PD-1 +T cells, and CD161 + lymphocytes. The magnitude of HBsAg decline was compared between the two groups. Results:The proportions of PD-1 + lymphocytes and CD8 +PD-1 +T cells in the IFN treatment group were significantly higher than those in the healthy control group and the non-IFN treatment group ( P<0.001). Moreover, the proportions of PD-1 + lymphocytes [IFN treatment group 48 weeks: 24.3 (23.7, 28.0)%, non-IFN treatment group: 12.7 (10.0, 18.5)%, P<0.01] and CD8 +PD-1 +T cells [IFN treatment group 48 weeks: 29.29 (26.73, 32.98)%, non-IFN treatment group: 17.69 (9.62, 20.68)%, P<0.05] were higher in the IFN treatment group than those in the non-IFN treatment group at 48 weeks. The proportion of CD8 +CD161 +T cells was significantly lower in patients treated with IFN than in the non-IFN treatment group ( P<0.05) at 24 and 48 weeks, with no statistically significant difference with the healthy control group ( P>0.05). In the IFN treatment group, patients with high levels of PD-1 + and CD8 + PD1 lymphocytes had a significantly lower HBsAg decline compared to low-level patients, whereas no significant correlation was found between CD161 levels and HBsAg decline [PD-1 + lymphocytes: 0.15 (0.02, 0.18) log 10 IU/mL vs. 0.32 (0.13, 0.42) log 10 IU/mL, P<0.01; CD8 +PD-1 +T cells: 0.16 (0.03, 0.17) log 10 IU/mL vs. 0.34 (0.13, 0.44) log 10 IU/mL, P<0.05]. Conclusion:The proportions of CD8 +PD-1 +T cells and CD8 +CD161 +T cells were significantly regulated by PEG-IFN-α therapy in the peripheral blood of patients with CHB, revealing the important role of T cell immune activation status during antiviral treatment. The gradual decline of HBsAg is closely related to the high expression of PD-1, suggesting that PD-1 may be negatively regulated during the process of T cell exhaustion and immunological evasion.

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

Objective:To explore the efficacy and safety profile of tenofovir alafenamide fumarate (TAF) in the treatment of patients with decompensated hepatitis B cirrhosis.Methods:A two-way cohort study method was used to enroll patients with decompensated hepatitis B cirrhosis who visited four medical centers, including Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, from April 2021 to April 2024 and were treated with TAF and followed up for 48 weeks. The primary efficacy indicator was hepatitis B virus (HBV) DNA seronegative conversion rate at 48-weeks, and the secondary efficacy indicator was alanine aminotransferase (ALT) return to normal rate at 48-weeks. Relevant safety indicators, adverse drug reactions (ADRs), and clinical adverse outcomes were collected.Results:A total of 74 cases were included. Of these, 52 were males with an average age of (53.14 ± 9.15) years. Twenty-five and thirty-three cases completed 24 and 48 weeks of follow-up, respectively. The HBV DNA negative conversion rate was 96.97% (32/33), which was higher than the baseline of 58.1% (43/74) following 48 weeks of TAF treatment. The ALT return to normal rate was 72.73% (24/33), which was higher than the baseline of 47.30% (35/74); however, the renal function and blood lipid levels did not change significantly compared with the baseline level after completing 48 weeks of treatment (P>0.05). During the follow-up period, one case developed hepatocellular carcinoma, and no other adverse clinical outcomes, such as liver transplantation or death, were reported.Conclusion:TAF has a good efficacy and safety profile in the treatment of patients with decompensated hepatitis B cirrhosis.

Objective:To explore the efficacy and safety profile of tenofovir alafenamide fumarate (TAF) in the treatment of patients with decompensated hepatitis B cirrhosis.Methods:A two-way cohort study method was used to enroll patients with decompensated hepatitis B cirrhosis who visited four medical centers, including Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, from April 2021 to April 2024 and were treated with TAF and followed up for 48 weeks. The primary efficacy indicator was hepatitis B virus (HBV) DNA seronegative conversion rate at 48-weeks, and the secondary efficacy indicator was alanine aminotransferase (ALT) return to normal rate at 48-weeks. Relevant safety indicators, adverse drug reactions (ADRs), and clinical adverse outcomes were collected.Results:A total of 74 cases were included. Of these, 52 were males with an average age of (53.14 ± 9.15) years. Twenty-five and thirty-three cases completed 24 and 48 weeks of follow-up, respectively. The HBV DNA negative conversion rate was 96.97% (32/33), which was higher than the baseline of 58.1% (43/74) following 48 weeks of TAF treatment. The ALT return to normal rate was 72.73% (24/33), which was higher than the baseline of 47.30% (35/74); however, the renal function and blood lipid levels did not change significantly compared with the baseline level after completing 48 weeks of treatment (P>0.05). During the follow-up period, one case developed hepatocellular carcinoma, and no other adverse clinical outcomes, such as liver transplantation or death, were reported.Conclusion:TAF has a good efficacy and safety profile in the treatment of patients with decompensated hepatitis B cirrhosis.

【Objective】 To study the expression levels of suppressor of cytokine signaling 1 (SOCS1) and its clinical significance in hepatitis B virus (HBV)-related liver diseases. 【Methods】 For this study we enrolled 25 patients with chronic hepatitis B (CHB), hepatitis B cirrhosis, or HBV-associated chronic acute liver failure (HBV-ACLF), and 25 healthy controls. The expression levels of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) were determined using the RT-PCR method. The levels of SOCS1 and interleukin-6 (IL-6) in the plasma of patients with chronic liver diseases and healthy controls were measured using the ELISA method. The relative expression levels of SOCS1, SOCS1 mRNA, and other laboratory test indicators such as HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin activity (PTA) and total bilirubin (TBil) were compared among the groups. Additionally, the correlation between the expression levels of SOCS1 mRNA and the aforementioned laboratory indicators was assessed. 【Results】 The expression levels of SOCS1 mRNA and serum SOCS1 were highest in the HBV-ACLF group, followed by the cirrhosis group, and lowest in the healthy control group, with statistically significant differences (F=109.65, P<0.001). The relative expression of SOCS1 mRNA was positively correlated with TBil (r=0.89, P<0.001), ALT (r=0.89, P<0.001), AST (r=0.84, P<0.001) and IL-6 (r=0.93, P<0.001), but negatively correlated with PTA (r=-0.89, P<0.001) and was not significantly correlated with HBV-DNA (P=0.28). 【Conclusion】 The expression levels of SOCS1 in patients with HBV-related chronic liver diseases can reflect the severity of the disease and show a significant correlation with indicators used to assess the severity of liver diseases.

Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.

Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.