Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Analysis of clinical characteristics of thyroid disorders in patients with chronic hepatitis B treated with pegylated-interferon alpha.

BACKGROUND: Thyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy. METHODS: In this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed. RESULTS: During the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels. CONCLUSIONS: TD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.

Duration of SARS-CoV-2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID-19.

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.

Durability of Interferon-induced Hepatitis B Surface Antigen Seroclearance.

Hepatitis B surface antigen (HBsAg) seroclearance has been recommended as an optimal endpoint of antiviral treatment by the latest chronic hepatitis B management guideline.1 However, few reports investigated the durability of response after HBsAg seroclearance, because of a lower HBsAg seroclearance rate and the difficulty of obtaining a sufficient number of samples for analysis. Our center has made a long-term commitment to investigate the personalized antiviral therapy for chronic hepatitis B. More than 300 patients achieved HBsAg seroclearance by interferon (IFN)-based antiviral treatment. In this study, the durability and the effects of hepatitis B virus (HBV) surface antibody (Anti-HBs) level on relapse after HBsAg seroclearance were investigated.

A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha.

Hepatitis B surface antigen (HBsAg) clearance represents a clinical cure, although the clearance rate is extremely low. The aim of this study was to evaluate the feasibility and safety profiles of pegylated-interferon α-2a (PEG-IFNα-2a) as a therapeutic option for inactive HBsAg carriers. There were 144 inactive HBsAg carriers enrolled and divided into a therapeutic group (102 subjects) and a control group (42 subjects). PEG-IFNα-2a and PEG-IFNα-2a combined with adefovir dipivoxil were used for treatment group subjects with hepatitis B virus DNA <20 IU/mL and 20 IU/mL ≤ hepatitis B virus DNA < 2,000 IU/mL, respectively. Total therapy duration was no more than 96 weeks. HBsAg clearance and seroconversion rates at therapeutic weeks 48 and 96 were used to evaluate the therapeutic efficacy. Per protocol analysis showed that the HBsAg clearance rate and seroconversion rate in the treatment group were 29.8% and 20.2% at week 48 and increased to 44.7% and 38.3% at week 96, respectively. However, the HBsAg clearance rate in the control group was 2.4% at weeks 48 and 96, and no subject achieved seroconversion. The quantitative HBsAg levels and changes during the early period of treatment (at week 12 and week 24) as well as the alanine aminotransferase elevation at week 12 were strong predictors of HBsAg clearance. The adverse events were similar to those with treatment for chronic hepatitis B patients. CONCLUSION: High rates of HBsAg clearance and seroconversion could be achieved by PEG-IFNα-2a-based treatments and the treatments were relatively safe for inactive HBsAg carriers. (Hepatology 2017;66:1058-1066).

[Efficacy of combination antiviral therapy following childbirth in pregnant HBV carriers receiving telbivudine for prevention of mother-to-child transmission].

OBJECTIVE: To observe the clinical efficacy of combination therapy with peg-IFNalpha and adefovir (CPIA) in women who were hepatfis B virus (HBV) carriers and had just given birth and received telbivudine (LdT) during pregnancy for prevention of mother-to-child transmission. METHODS: One-hundred-and-fifty third trimester-pregnant women who were HBV carriers with highly-viremic were treated with LdT until time of birth. After delivery, those women with alanine aminotransferase (ALT) level exceeding two times the upper limit of normal and HBV DNA level that had decreased more than 31 gIU/mL or hepatitis B e antigen (HBeAg) titer that had decreased more than 50% were switched to CPIA for 96 weeks. RESULTS: Following delivery, 45 of the women were switched to the CPIA treatment, of which 91.1% (41/45) achieved virological response, 55.6% (25/45) achieved HBeAg clearance or seroconversion, and 26.7% (12/45) achieved hepatitis B surface antigen (HBsAg) clearance or seroconversion.The immediate post-delivery (and pre-CPIA) levels of HBeAg and HBV DNA were negatively associated with HBeAg clearance. Ninety-eight of the total study participants stopped the LdT treatment and there were no cases of significant deterioration of liver function. CONCLUSION: Pregnant women who are HBV carriers and receive LdT for protection against mother-to-child transmission, and who show significant ALT elevation and decreased HBeAg titer and/or reduced HBV DNA after delivery, may be good candidates for the CPIA therapy following delivery.

The Apelin/APJ System: A Potential Therapeutic Target for Sepsis.

Apelin is the native ligand for the G protein-coupled receptor APJ. Numerous studies have demonstrated that the Apelin/APJ system has positive inotropic, anti-inflammatory, and anti-apoptotic effects and regulates fluid homeostasis. The Apelin/APJ system has been demonstrated to play a protective role in sepsis and may serve as a promising therapeutic target for the treatment of sepsis. Better understanding of the mechanisms of the effects of the Apelin/APJ system will aid in the development of novel drugs for the treatment of sepsis. In this review, we provide a brief overview of the physiological role of the Apelin/APJ system and its role in sepsis.

A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets.

Background: HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. Methods: In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. Result: From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Conclusions: Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection.

Bone marrow suppression or active proliferation? An analysis of neutropenia after pegylated interferon treatment of patients with chronic hepatitis C.

BACKGROUND: Neutropenia is a common adverse effect of the treatment of chronic hepatitis C with pegylated interferon and ribavirin. However, the mechanism involved is unknown. The present study aimed to investigate the cause of treatment-induced neutropenia by determining cytokine levels in plasma and in bone marrow smears. METHODS: Fifteen patients with chronic hepatitis C were enrolled in this study. Plasma cytokine levels were determined using the Luminex assay before and during treatment. We simultaneously determined the levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and 7 other cytokines, and performed bone marrow cytology when blood cell counts indicated neutropenia. RESULTS: Only 1 bone marrow smear indicated a low cell proliferation level, whereas active proliferation was observed in the remaining 14 patients. The levels of G-CSF, GM-CSF, interleukin (IL)-2, IL-4, IL-6, and interferon (IFN)-γ decreased significantly in patients with neutropenia (p < 0.05). In contrast, the levels of IL-8, IL-10, and tumor necrosis factor (TNF)-α showed no significant change (p = 0.713, 0.930, 0.833, respectively) before or after treatment. CONCLUSIONS: The bone marrow of most patients with IFN-induced neutropenia showed active cell proliferation. Elevated G-CSF and GM-CSF but not bone marrow suppression was observed along with neutropenia after pegylated interferon treatment, suggesting a causative role of G-CSF and GM-CSF in neutropenia.

[Efficacy and safety of peginterferon alfa-2a (40 kd) plus adefovir for 96 weeks in HBeAg-negative chronic hepatitis B patients].

OBJECTIVE: To investigate the efficacy and safety of an extended course (96-week) of combination treatment with peginterferon alfa-2a (Peg-IFNa-2a; 40 kd] plus adefovir (ADV) for treating chronic hepatitis B (CHB) in Chinese patients with negativity for hepatitis B e antigen (HBeAg). METHODS: A total of 25 consecutive patients with HBeAg-negative CHB were administered Peg-IFNa-2a (135-180 mug/week) plus ADV (10 mg/day) for 96 weeks. All patients were followed-up for 24 weeks after treatment completion. Levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HbsAg) were measured by fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescent microparticle immunoassay, respectively, at 12-week intervals throughout the treatment course and at the end-of-follow-up (week 120). Patients underwent serological analysis at 3-6 month intervals during treatment and follow-up to evaluate occurrence of adverse events; serological parameters included blood count, markers of liver, kidney and thyroid function, and levels of autoantibodies and creatine kinase. RESULTS: For all patients, the 96-week course of Peg-IFNa-2a plus ADV reduced the level of HBV DNA below the detection threshold (less than 500 copies/ml by FQ-PCR). The overall rate of HBsAg seroconversion was 12% (3/25) at week 48, 28% (7/25) at week 96, and 32% (8/25) at week 120. The occurrences of adverse events were similar at week 48 and week 96. CONCLUSION: The extended-course Peg-IFNa-2a plus ADV combination therapy achieved a 100% virological response and better rates of HBsAg seroconversion than 48 weeks of therapy, without a decrease in safety.

Hepatitis B virus infection combined with nonalcoholic fatty liver disease: Interaction and prognosis.

Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.

MBOAT7 rs641738 (C>T) is associated with NAFLD progression in men and decreased ASCVD risk in elder Chinese population.

Background and aim: The MBOAT7 rs641738 (C>T) variant has demonstrated an association with non-alcoholic fatty liver disease (NAFLD) in both adult and pediatric patients, while few studies have been conducted in elderly populations. Hence, a case-control study was undertaken to assess their correlation in elderly residents in a Beijing community. Materials and methods: A total of 1,287 participants were included. Medical history, abdominal ultrasound, and laboratory tests were recorded. Liver fat content and fibrosis stage were detected by Fibroscan. Genotyping of genomic DNA was performed using the 96.96 genotyping integrated fluidics circuit. Results: Of the recruited subjects, 638 subjects (56.60%) had NAFLD, and 398 subjects (35.28%) had atherosclerotic cardiovascular disease (ASCVD). T allele carriage was associated with higher ALT (p=0.005) and significant fibrosis in male NAFLD patients (p=0.005) compared to CC genotype. TT genotype was associated with reduced risk of metabolic syndrome (OR=0.589, 95%CI: 0.114-0.683, p=0.005) and type 2 diabetes (OR=0.804, 95%CI: 0.277-0.296, p=0.048) in NAFLD population when compared to the CC genotype. In addition, TT genotype was also associated with reduced risk of ASCVD (OR=0.570, 95%CI:0.340-0.953, p=0.032) and less obesity (OR=0.545, 95%CI: 0.346-0.856, p=0.008) in the whole population. Conclusion: MBOAT7 rs641738 (C>T) variant was associated with fibrosis in male NAFLD patients. The variant also reduced risk of metabolic traits and type 2 diabetes in NAFLD and ASCVD risk in Chinese elders.

Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure.

Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Potent hepatitis B surface antigen response to treatment of hepatitis-B-e-antigen-positive chronic hepatitis B with α-interferon plus a nucleos(t)ide analog.

BACKGROUND AND AIM: Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with α-interferon (IFN-α) and a nucleos(t)ide analog. METHODS: This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment. RESULTS: A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3-60 months) and 25.5 months (range 9-63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). CONCLUSIONS: Extended treatment with IFN-α in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance-the closest outcome to cure.

[Efficacy of low-dose interferon therapy for treating chronic hepatitis C patients who cannot tolerate standard treatment].

OBJECTIVE: To investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment. METHODS: Forty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks. RESULTS: Forty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis. CONCLUSIONS: Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.

Study on the Retreatment, Outcome, and Potential Predictors of Recurrence in Patients With Recurrence of Hepatitis B After Functional Cure.

Background: Studies about the retreatment and predictors for patients with hepatitis B recurrence after functional cure are rare. This study aimed to evaluate the effect of retreatment, outcome, and potential predictors of recurrence in patients with recurrence after functional cure. Methods: A long-term follow-up was conducted with 32 cumulatively obtained patients who relapsed after cessation of pegylated interferon (Peg-IFN)-based antiviral treatment. The decision of whether to treatment or which therapeutic method to use [Peg-IFN or nucleos(t)ide analogs (NAs)] was based on the patient's preferences and wishes. The rate of achieving functional cure and the clinical outcomes of different therapeutic methods were analyzed. Hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) levels were detected in patients with blood samples during follow-up to evaluate the predictive ability of recurrence. Results: The follow-up time of 32 recurrence cases was 42-532 weeks after recurrence (median 226 weeks). In the 20 patients who received retreatment (15 received Peg-IFN and 5 received NAs only), the rate of functional cure was 65.0% (13/20); it was 86.7% (13/15) in the patients retreated with Peg-IFN. Three cases experienced recurrence again. Five patients received NA treatment, and no functional cure was achieved. No drug intervention was administered for 12 patients, 2 of them with hepatitis B virus (HBV) DNA spontaneous clearance, and one patient achieved spontaneous hepatitis B surface antigen (HBsAg) clearance during follow-up. Patients who relapsed after functional cure with Peg-IFN treatment did not have liver cirrhosis or hepatocellular carcinoma during the follow-up, regardless of whether they received retreatment. Anti-HBs and anti-HBc levels at the end of therapy were predictors of recurrence (p < 0.001, p = 0.023). The value of combining the above two indicators in predicting recurrence was further improved, the areas under the receiver operating characteristic curves were 0.833, at combining predictors >-0.386, the predictive sensitivity and specificity for recurrence were 86.67% and 90.62%. Conclusion: The functional cure rate was above 80% for patients with recurrence treated by Peg-IFN. During the follow-up, liver cirrhosis and hepatocellular carcinoma were not observed in all recurrence cases. High levels of anti-HBs and anti-HBc at the time of drug discontinuation are less likely to relapse.

Serum hepatitis B virus large and medium surface proteins as novel tools for predicting HBsAg clearance.

Background: There is still lack of reliable predictors for hepatitis B surface antigen (HBsAg) clearance. Recent studies have shown that the levels of large (LHBs) and medium hepatitis B surface proteins (MHBs) are closely related to antiviral efficacy. This study aimed to investigate the possibility of LHB and MHB levels to predict HBsAg clearance. Methods: An inactive HBsAg carriers (IHCs) cohort that had received pegylated interferon (Peg-IFN) treatment was divided into the HBsAg-cleared group (R group) and the HBsAg non-cleared group (NR group) based on whether HBsAg was cleared at 96 weeks. We detected the levels of LHBs and MHBs to evaluate the possibility of predicting HBsAg clearance. Results: There were 39 patients in the R group and 21 in the NR group. The total HBsAg, LHB, and MHB levels at baseline and at 12 weeks were significantly lower in the R group than in the NR group (all p< 0.05). Multivariate logistic regression indicated that LHB and MHB levels at baseline and 12 weeks were independent predictors of HBsAg clearance (OR = 0.435, p = 0.016; OR = 0.136, p = 0.003; OR = 0.137, p = 0.033; OR = 0.049, p = 0.043). The area under the curve (AUC) for the baseline and 12-week LHB and MHB levels was 0.827-0.896, which were greater than that of the total HBsAg level at baseline and 12-week (AUC: 0.654-0.755). Compared with the prediction results of a single indicator, the combination of LHB and MHB levels had better value in predicting HBsAg clearance. The AUCs of combination factor 1, constructed from baseline LHB and MHB, and combination factor 2, constructed from 12-week LHB and MHB, were 0.922 and 0.939, respectively, and the sensitivity (82.05%-100.00%) and specificity (85.71%-100.00%) were both high. The combined indicators based on baseline LHBs ≤ 13.99 ng/mL and MHBs ≤ 7.95 ng/mL predicted HBsAg clearance rate of more than 90%. Conclusion: Baseline and 12-week LHB and MHB levels can predict HBsAg clearance obtained by Peg-IFN therapy in IHCs, and the predictive value is higher than that of the total HBsAg levels.

Clinical cure rate of inactive HBsAg carriers with HBsAg <200 IU/ml treated with pegylated interferon.

Purpose: HBsAg clearance represents clinical cure for patients with hepatitis B, but remains difficult to obtain for most HBV-infected patients. Recent studies have shown that inactive HBsAg carriers treated with pegylated interferon can achieve higher clinical cure rates, which may imply that the lower the baseline HBsAg quantification, the higher HBsAg clearance rate. Therefore, this study further investigated the HBsAg clearance rate in inactive HBsAg carriers with low level of HBsAg (<200 IU/ml) treated with pegylated interferon. Methods: This is a prospective cohort study. Inactive HBsAg carriers with HBsAg<200 IU/ml were divided into treatment and control groups. Pegylated interferon was administered to the patients in therapeutic group for 96 weeks. The patients in control group underwent 96 weeks of observation without any anti-viral treatment. All patients were tested for HBsAg, anti-HBs, HBV DNA, liver function, blood count, thyroid function, thyroid antibodies and autoantibodies at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96. Controlled attenuation parameter (CAP) and liver stiffness measure (LSM) were evaluated at baseline and week 96. Patients were classified into no steatosis, mild steatosis, moderate steatosis and severe steatosis according to the value of CAP. Results: A total of 174 inactive HBsAg carriers with HBsAg<200IU/ml were enrolled, including 84 in the treatment group and 90 in the control group. In the treatment group, HBsAg clearance rate was 30.77% (24/78) at week 48, and increased to 57.69% (45/78) at week 96. HBsAg clearance occurred in 2 patients with a clearance rate of 2.27% (2/88) in control group, The HBsAg clearance rate of the treatment group was significantly higher than that of the control group (P<0.001). HBsAg clearance was significantly higher in patients with moderate steatosis than in those without steatosis (74.07% vs. 48.15%, p=0.008) at week 96. Conclusion: High HBsAg clearance rate could be obtained for inactive HBsAg carriers with HBsAg< 200 IU/ml treated with peginterferons. Inactive HBsAg carriers with moderate hepatic steatosis are more sensitive for the treatment.

Low Level of Serum Immunoglobulin G Is Beneficial to Clinical Cure Obtained With Pegylated Interferon Therapy in Inactive Surface Antigen Carriers.

Purpose: Our recent study showed a high rate of HBsAg clearance in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To better understand the immune-mediated component of HBsAg clearance, this study investigated the role of serum immunoglobulin G (IgG) and its subclasses in predicting HBsAg clearance in IHCs with PEG-IFN therapy. Methods: In this study, IHCs received PEG-IFN for 96 weeks. Subjects who achieved clearance of HBsAg were considered responders (R group), and those in whom HBsAg was not cleared were considered non-responders (NR group). The HBsAg, ALT, and serum lgG subtypes (lgG1, IgG2, IgG3, lgG4) were tested at baseline, and at 12 and 24 weeks of treatment. To evaluate the factors in predicting HBsAg clearance, univariate and multivariate logistic regression analyses were performed. The receiver operator characteristic curves and the area under the receiver operator characteristic curve (AUROC) were used to evaluate prognostic values. Results: Our results showed that 39 cases obtained HBsAg clearance (group R), while 21 cases did not (group NR). There was no significant difference in age, ALT, and AST levels between the two groups. The serum levels of IgG1, lgG2, lgG3 and lgG4 at baseline, and at 12 and 24 weeks were significantly lower in IHC with HBsAg clearance than in the NR group. Univariate logistic regression analysis showed that serum IgG1, IgG2, IgG3, and IgG4 levels at baseline, and at 12, and 24 weeks were all strong predictors of HBsAg clearance. In all indicators, lgG2 had the highest AUROC at baseline and lgG3 the highest AUROC at week 12. A multifactor logistic analysis was performed with y=33.933-0.001*BaselinelgG1-0.002*BaselinelgG2. The area under the curve was 0.941 with 100% sensitivity and 76.19% specificity. Conclusion: Together, our findings suggest that serum IgG has a higher predictive value compared to the convention predictors of HBsAg and ALT for HBsAg clearance and thus may be a better clinical predictor of HBsAg clearance in IHCs.

Clinical Features and T Cell Immune Characteristics of Postpartum Hepatitis Flare in Pregnant Women With HBeAg-Positive Chronic HBV Infection.

Background: The extent of the increase in postpartum alanine transaminase (ALT) varies significantly among pregnant women in the immune tolerance stage of nucleoside analogue (NA) intervention, so this study is an attempt to analyze the clinical features of patients with and without postpartum hepatitis flare and preliminarily explore the differences in their immune functions. Methods: Pregnant women with a gestational age of 24-28 w and in the immune tolerance stage of NA intervention for hepatitis B virus (HBV) infection were included and divided into a hepatitis group (Group 1) and a nonhepatitis group (Group 2) according to the ALT level at 6-12 w after childbirth. The clinical features were analyzed, and the phenotypes, functions, and cytokines of clusters of differentiation CD8+ T cells in the two groups of patients were detected using flow cytometry before and after childbirth. Results: A total of 15 patients with postpartum hepatitis flare were enrolled in Group 1, and 10 matched patients were selected as controls for Group 2. Compared with the individuals in Group 2, the postpartum clinical features in Group 1 included a remarkable elevation of the ALT level on the basis of a relatively low HBV DNA level, usually accompanied by a decline in hepatitis B virus surface antigen levels as well as HBeAg levels. In addition, CD8+ T cell activation was enhanced after childbirth in Group 1. In particular, there was a notable difference in the activation of TEMRA subsets, and the frequency of CD8+ T cells expressing perforin and granzyme B increased. Conclusion: The changes in the immune characteristics of CD8+ T cells may play a certain role in breaking down immune tolerance in patients with postpartum hepatitis flare, and the indexes related to activating and killing functions may help to indicate the population with hepatitis flare after childbirth.