The Predictive Value of Baseline HBs Ag Level and Early Response for HBs Ag Loss in Patients with HBe Ag-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment

Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Treatment of Hepatitis C with Pegylated Interferon Alpha-2a and Ribavirin:Experience from Benin

Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.

Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

Background： Hepatitis B surfhce antigen （HBsAg） Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B （CHB）. This study aimed to assess the patterns of ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon （PEG-IFN） α-2a. Methods： A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen （H BeAg）-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators （HBsAg, anti-HBs, HBeAg, and anti-HBe） were determined before and every 3 months during PEG-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results： Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3%, and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients （2.9 ± 1.1 log 1U/ml） compared with HBeAg-negative patients （2.0 ± 1.3 log I U/ml; t = 4.733, P 〈 0.001）, but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions： Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.

Improved Sustained Virological Response Following Treatment with Pegylated-Interferon Alpha-2b Compared with Alpha-2a, Both with Ribavirin, for Chronic Hepatitis C Infection with Genotypes 2 and 3

Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate analysis of prospectively collected treatment data from two tertiary centres on 351 treatment na?ve HCV Genotype 2 or 3 patients who received PEG-IFa-2a or b plus ribavirin. Results: Univariate analyses demonstrate that PEG-IFa-2b based on regimens achieved a higher sustained virological response (SVR) than PEG-IFa-2a (77.9% versus 62.0%, P = 0.0012). On multivariate analyses, PEG-IFa-2b appeared superior to PEG-IFa-2a with an odds ratio (OR) and 95% confidence interval (CI95) for SVR of 2.19 (CI95 1.35-3.52, P = 0.0005). Genotype was a significant predictor of outcome in the multivariate model with 80% of Genotype 2 but only 67.7% of Genotype 3 subjects achieving SVR (OR 2.66 [CI95 1.35-5.92]). Increasing age was negatively associated with SVR (OR 0.97 [CI95 0.94-0.99]). Some of the differences in SVR are explained by higher relapse rates with PEG-IFa-2a (P = 0.009). Conclusions: PEG-IFa-2b and RBV achieve higher SVR rates than PEG-IFa-2a and RBV in Genotypes 2 and 3 chronic HCV infections. There is less relapse with PEG-IFa-2b. Genotype 2 infections are considerably easier to cure. SVR is higher in younger patients. These findings should influence a choice of PEG-IFa in the era of direct acting anti-viral drugs in therapy of Genotypes 2 and 3.

Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效观察

目的:探讨聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的临床疗效及安全性。方法:选取2014年1月—2017年1月嘉应学院医学院附属医院收治的慢性丙型肝炎患者100例,以计算机随机数字分组法分为对照组和观察组,每组50例。对照组采用普通干扰素α-1b联合利巴韦林治疗,观察组采用聚乙二醇干扰素α-2a联合利巴韦林治疗,比较两组患者的临床疗效、病毒学应答率、肝功能及不良反应发生情况。结果:观察组患者的总有效率为84%(42/50),明显高于对照组的62%(31/50);观察组患者的快速病毒学应答率、早期病毒学应答率和治疗终点病毒学应答率明显高于对照组,差异均有统计学意义(P<0.05)。治疗后,两组患者的丙氨酸氨基转移酶、天门冬氨酸氨基转移酶和碱性磷酸酶等肝功能指标水平均明显低于本组治疗前,且观察组患者明显低于对照组,差异均有统计学意义(P<0.05);两组患者不良反应发生率的差异无统计学意义(P>0.05)。结论:聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎,疗效显著,安全可靠。

HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b

Background： We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens （HBcrAg） for predicting hepatitis B e antigen （HBeAg） seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon （IFN） alfh-2b or pegylated IFN. Methods： Fifty-eight patients were enrolled： 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up （LTFU）, during which time the dynamics of the HBcrAg was monitored. Results： The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group （from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were II0,245 kU/ml, 3760 kU/ ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively）. HBcrAg 〈19,565 kU/ml at week 24, HBcrAg 〈34,225 kU/ml at 12-week follow-up, and HBcrAg decrease 〉0.565 log10 kU/ml from the baseline to the end of treatment （EOT） had negative predictive values （NPVs） of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values （PPVs） were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions： Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory （all 〈31%）. The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.

α-2-HS-glycoprotein is a potential marker predicting hepatitis B e antigen seroconversion in patients with chronic hepatitis B during treatment with pegylated interferon alfa-2b

The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.

Clinical characteristics of null responders to Peg-IFNα2b/ ribavirin therapy for chronic hepatitis C

AIM: To predict which chronic hepatitis C patients are likely to be late-responders, we herein investigated the clinical characteristics of null-responders at 36 wk with hepatitis C virus (HCV) genotype Ib and a high viral load during the course of pegylated interferon (Peg-IFN)/ ribavirin ther apy. METHODS: One hundred forty-two patients with genotype Ib HCV and a high viral load were included in this study. Peg-IFNα2b (1.5 μg/kg once a week) and ribavirin (600-1000 mg per day according to body weight) were administered for 48 wk. We def ined nullresponders as the cases that never cleared serum HCV RNA as determined using RT-PCR until 36 wk. Other patients were def ined as responders. We compared the clinical characteristics (age, gender, body mass index, previous treatment) and HCV RNA titer during the therapy between null-responders and responders.RESULTS: The HCV RNA clearance rate was 17.9% (24/134), 46.3% (62/134), 60.6% (86/142), 86.6% (123/142), and 88.0% (125/142) at 4, 8, 12, 24, and 36 wk, respectively. There were 17 patients (12.0%) who were still null-responders at 36 wk. There were no differences in the clinical characteristics between the responders and null-responders except for the titer and decline rates of HCV RNA at 1 wk and 4 wk. The HCV RNA titers at 1 wk and after 4 wk of treatment were significantly higher in the null-responders in comp arison to the responders (P <0.01). The serum HCV RNA titers of the responders decreased by 1.3 log after 1 wk of treatment, and 1.6 log after 4 wk of treatm ent, respectively. On the other hand, the titers of the null responders decreased by only 0.5 log after 1 wk, and 0.7 log after 4 wk of treatment, respectively. The decrease rates of HCV RNA after 1 and 4 wk of treatm ent were signif icantly worse for null responders than for the responders (P <0.01). CONCLUSION: The HCV RNA titer at 1 wk and 4 wk after initiating treatment may be useful for predicting null-responders to Peg-IFNα2b/ribavirin therapy. However, further investigation is needed to determine the optimal time at which the decision to discontinue the Peg-IFNα2b/ribavirin therapy for null-responders can be made.

聚乙二醇干扰素α-2a治疗新型冠状病毒感染:反复核酸阳性超过3个月2例报告

目的 探讨新型冠状病毒感染(新冠)核酸反复阳性时间持续3个月以上患者的治疗方法。方法 回顾性分析2例使用聚乙二醇干扰素α-2a治疗的新冠复阳患者的临床资料。结果 2例患者均为中年男性,分别诊断为新冠轻型和普通型,前期经过干扰素α-2b抗病毒、调节免疫、中药等药物治疗后,鼻咽拭子核酸结果显示反复阳性,时间超过3个月。予聚乙二醇干扰素α-2a抗病毒治疗,2例患者分别于治疗2周及6周后病毒核酸转阴,治疗过程中未见不良反应。结论 聚乙二醇干扰素α-2a治疗可为治疗新冠长时间复阳患者提供一种治疗策略。

抗病毒治疗对慢性丙型肝炎合并2型糖尿病预后的影响

目的:研究聚乙二醇干扰素(Peg-IFNα)联合利巴韦林(RBV)抗病毒治疗对慢性丙型肝炎合并2型糖尿病患者预后的影响。方法:选择2008年1月~2015年10月我院门诊及住院慢性丙型肝炎合并2型糖尿病患者20例为研究组,20例非合并糖尿病的慢性丙型肝炎患者为对照组,2组均予Peg-IFNα-2a联合RBV治疗48周,研究组同时给予胰岛素降糖治疗。治疗过程中监测并分析2组4、12、48周时HCV RNA水平和持续病毒学应答率(SVR)、血液生化指标(ALT、TBIL、ALT、GGT)、肝纤维化标记物(LN、CIV、HA、CG)及空腹血糖情况。结果:研究组SVR为65%,与对照组相比差异无统计学意义。疗程结束后,2组血液生化指标、肝纤维化标记物均较前改善(P<0.05)。研究组治疗前空腹血糖为(7.96±2.34)mmol/L,治疗后为(8.03±1.36)mmol/L,差异无统计学意义(P>0.05)。结论:抗病毒治疗对慢性丙型肝炎合并2型糖尿病患者的治疗是安全有效的。

Frequency ofT-cell FoxP3＋ Treg and CD4＋/CD8＋ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon

Background Host immune responses against hepatitis B virus （HBV） induced by antiviral therapy play a crucial role in viral clearance. To further investigate the immune mechanisms underlying the differences between respondents and non-respondents, we analyzed myeloid dendritic cells （mDCs）, plasmacytoid dendritic cells （pDCs）, FoxP3＋ regulatory T cells （FoxP3＋ Treg） and programmed death 1 （PD-1） expression in CD4＋/CD8＋ T cells in chronic hepatitis B patients undergoing pegylated interferon （PeglFN）α-2b treatment. Methods Patients received PeglFNα-2b for 24 or 48 weeks, with follow-up at 24 weeks. The frequencies of mDCs, pDCs, FoxP3＋ Treg, and PD-1 expression by CD4＋/CD8＋ T cells were evaluated by flow cytometry at baseline, weeks 4 and 12, end of treatment, and follow-up （12/24 weeks）. Results In HBeAg seroconverters （respondents）, the mDC relative frequency decreased at week 4 and then rebounded at week 12. The pDC relative frequency decreased consistently. In non-HBeAg seroconverters （non-respondents）, both mDC and pDC frequencies decreased slightly. The FoxP3＋ Treg relative frequency decreased during treatment and remained low during follow-up in respondents, while in non-respondents it decreased slightly during therapy but rebounded after discontinuation. In patients with HBeAg 〈17.55 PEI-U/ml at week 12 and 〈8.52 PEI-U/ml at week 24, the FoxP3＋ Treg frequency decreased during treatment and at follow-up. In respondents, CD4~PD-1 and CD8＋PD-1 levels decreased at week 4 and remained low at week 12. In non-respondents, PD-1 expression decreased at week 4 but rebounded at week 12. Conclusions The results indicate that the dynamic changes in DCs, FoxP3＋ Treg frequency, and PD-1 expression by CD4＋ and CD8＋ T cells exhibit different trends in HBeAg and non-HBeAg seroconversion patients. During PeglFNa-2b treatment of chronic hepatitis B patients, these changes may be of predictive value for HBeAg seroconversion. HBsAg and HBeAg levels are related to FoxP3＋ Treg frequency.

胸腺肽肠溶片联合聚乙二醇干扰素对慢性肝炎患者的治疗效果及其相关指标的影响

目的探讨胸腺肽肠溶片联合聚乙二醇干扰素对慢性肝炎患者血清中CXC趋化因子受体3(CXCR3)、趋化因子受体6(CCR6)、血清白介素2(IL-2)、肝功能指标及其可溶性配体水平的影响。方法选取2017年9月~2018年9月我院接收的74例慢性肝炎患者,根据随机数字表法分为观察组与对照组,每组各37例。对照组仅接受胸腺肽肠溶片治疗,观察组接受胸腺肽肠溶片联合聚乙二醇干扰素治疗。比较两组患者治疗后的CXCR3、CCR6、清蛋白(ALB)、总胆红素(TBil)、丙氨酸氨基转移酶(ALT)、乙肝病毒脱氧核糖核酸(HBV-DNA)、乙肝表面抗原(HBsAg)、乙型肝炎E抗原(HBeAg)等病毒学指标水平。结果观察组患者治疗后的CXCR3、CCR6高于对照组,血清IL-2水平低于对照组;观察组患者治疗后的ALB水平高于对照组,TBil、ALT水平均低于对照组;观察组患者治疗后的HBV-DNA、HBsAg、HBeAg水平低于对照组,差异均有统计学意义(P<0.05)。结论慢性肝炎患者经胸腺肽肠溶片联合聚乙二醇干扰素治疗后,CXCR3、CCR6及血清IL-2水平可以有效降低,且肝功能及其可溶性配体水平显著改善,治疗效果确切。

Clinical cure and liver fibrosis reversal after postoperative antiviral combination therapy in hepatitis B-associated non-cirrhotic hepatocellular carcinoma: A case report

BACKGROUND The incidence of hepatocellular carcinoma(HCC)is high in China,and approximately 15%-20%of HCC cases occur in the absence of cirrhosis.Compared with patients with cirrhotic HCC,those with non-cirrhotic HCC have longer postoperative tumor-free survival.However,the overall survival time is not significantly increased,and the risk of postoperative recurrence remains.Strategies to improve the postoperative survival rate in these patients are currently required.CASE SUMMARY A 47-year-old man with a family history of HCC was found to have hepatitis B virus(HBV)infection 25 years ago.In 2000,he was administered lamivudine for 2 years,and entecavir(ETV 0.5 mg)was administered in 2006.In October 2016,magnetic resonance imaging revealed a tumor in the liver(5.3 cm×5 cm×5 cm);no intraoperative hepatic and portal vein and bile duct tumor thrombi were found;and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis(G1S3).ETV was continued,and no significant changes were observed on imaging.After receiving pegylated interferon alfa-2b(PEG IFNα-2b)(180μg)+ETV in February 2019,the HBsAg titer decreased significantly within 12 wk.After receiving hepatitis B vaccine(60μg)in 12 wk,HBsAg serological conversion was realized at 48 wk.During the treatment,no obvious adverse reactions were observed,except for early alanine aminotransferase flares.The reexamination results of liver pathology were G2S1,and reversal of liver fibrosis was achieved.CONCLUSION The therapeutic regimen of ETV+PEG IFNα-2b+hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.

α-2-HS-糖蛋白对聚乙二醇干扰素alfa-2b治疗慢性乙型肝炎患者e抗原血清转换预测作用的研究

利用干扰素治疗慢性乙型肝炎仅在约1/3的患者中取得了满意的治疗效果.采用基于双向电泳的血清蛋白质组学技术,寻找慢性乙型肝炎患者干扰素治疗时发生e抗原血清学转换的预测标志物.对发生/未发生血清学转换组的患者基线和治疗24周血清进行差异蛋白的筛选和鉴定,并对筛选得到的α-2-HS-糖蛋白在训练组和验证组患者个体中进行了基线和第4周的进一步验证实验.结果发现,α-2-HS-糖蛋白从治疗基线至治疗第4周的变化趋势对慢性乙型肝炎患者干扰素alfa-2b治疗过程中e抗原血清学转换具有预测意义.

Study of recombinant human IFN-α-2b bacilli Calmette–Guerin activated killer cells and against bladder cancer cell in vitro

Presently,one of the most potent immunothera-pies is the application of bacillus Calmette Guerin(BCG)to prevent recurrences of the superficial bladder cancer.Despite its successful use,nonresponders and certain side effects remain a major obstacle.Therefore,current studies aim at developing recombinant BCG(rBCG)strains secreting Th1-like cytokines to improve the effectiveness of the therapy.In this study,a new type of rBCG strain constructed by Tianjin institute of Urology was tested for its immunostimulatory capacity in vitro.Peripheral blood monocytes(PBMC)were stimulated by recombinant BCG and transformed into bacilli Calmette–Guerin activated killer(BAK)cells,and the effect of anticancer BAK cells was studied.Recombinant IFN-a-2b-BCG,wild-type BCG(wBCG),wild-type BCG and IFN-a-2b were coincubated with PBMCs respectively in vitro,and the proliferation of PBMC was detected with MTT in different time.BAK cells have the ability to kill bladder tumor cells,and the antitumor activity of effecter cells was determined by LDH release assay.The result of MTT showed that the proli-feration of PBMC in the recombinant BCG group was more powerful than in the other two groups(P<0.05).The result of LDH release assay showed that the antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in all groups.We conclude that the recombinant BCG can activate more PBMCs to anti-bladder cancer in vitro than wild-type BCG does.