Predictive Value of Serum pgRNA on HBeAg Clearance in Patients with Chronic Hepatitis B with Low HBeAg Levels Treated with Pegylated Interferon

Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.

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.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients

AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.

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.

聚乙二醇干扰素α-2b联合替诺福韦对乙型肝炎患者肝功能及安全性的影响

目的:探讨聚乙二醇干扰素α-2b联合替诺福韦对乙型肝炎患者肝功能及安全性的影响。方法:选取2018年10月—2020年8月南阳医学高等专科学校第一附属医院收治的96例乙型肝炎患者作为研究对象,采用乱数表法分为A组和B组,每组各48例。A组给予替诺福韦酯片治疗,B组在A组基础上加用聚乙二醇干扰素α-2b治疗。比较两组患者治疗前、后总胆红素(TBIL)、白蛋白(ALB)、天门冬氨酸氨基转移酶(AST)、谷丙转氨酶(ALT)、干扰素-γ(IFN-γ)、白介素-10(IL-10)、白介素-4(IL-4)和白介素-2(IL-2)水平。比较两组患者乙型肝炎病毒(HBV)-DNA转阴率、乙型肝炎e抗原(HBeAg)转阴率、转换率和ALT复常率。统计两组患者治疗有效率和不良反应发生率。结果:治疗后,B组总胆红素(TBIL)、天门冬氨酸氨基转移酶(AST)和谷丙转氨酶(ALT)水平均低于A组,两组患者白蛋白(ALB)均升高且B组升高幅度大于A组,差异有统计学意义(t=15.629、27.253、30.580、11.761,P<0.05);治疗后,两组患者酶联免疫吸附测定干扰素-γ(IFN-γ)和白介素-2(IL-2)均升高,且B组升高幅度大于A组,白介素-10(IL-10)和白介素-4(IL-4)均降低,且B组降低幅度大于A组,差异有统计学意义(t=20.777、7.614、24.624、1.609,P<0.05);B组HBV-DNA转阴率、ALT复常率、乙型肝炎e抗原(HBeAg)转阴率、HBeAg转换率均高于A组,差异有统计学意义(χ^(2)=4.381、4.800、4.019、4.909,P<0.05);B组治疗总有效率高于A组,差异有统计学意义(χ^(2)=4.360,P<0.05);两组患者不良反应发生率比较,差异无统计学意义(χ^(2)=0.079,P>0.05)。结论:聚乙二醇干扰素α-2b联合替诺福韦可有效改善患者肝功能,调节免疫功能且安全性较高。

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.

Baseline HBsAg predicts response to pegylated interferon-α2b in HBeAg-positive chronic hepatitis B patients

AIM: To evaluate the predictive effect of baseline hepatitis B surface antigen(HBsAg) on response to pegylated interferon(PEG-IFN)-α2b in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients.METHODS: This retrospective analysis compared the treatment efficacy of PEG-IFN-α2b alone in 55 HBeAgpositive CHB patients with different baseline HBsAg levels. Serum HBV DNA load was measured at baseline, and at 12, 24 and 48 wk of therapy. Virological response was defined as HBV DNA < 1000 IU/mL. Serum HBsAg titers were quantitatively assayed at baseline, and at 12 and 24 wk.RESULTS: Eighteen patients had baseline HBsAg > 20 000 IU/mL, 26 patients had 1500-20000 IU/mL, and 11 patients had < 1500 IU/mL. Three(16.7%), 11(42.3%) and seven(63.6%) patients in each groupachieved a virological response at week 48, with a significant difference between groups with baseline HBsAg levels > 20000 or < 20000 IU/mL(P = 0.02). Thirteen patients had an HBsAg decline > 0.5 log10 and 30 patients < 0.5 log10 at week 12; and 6(46.2%) and 10(33.3%) in each group achieved virological response at week 48, with no significant difference between the two groups(P = 0.502). Eighteen patients had an HBsAg decline > 1.0 log10 and 30 patients < 1.0 log10 at week 24, and 8(44.4%) and 11(36.7%) achieved a virological response at week 48, with no significant difference between the two groups(P = 0.762). None of the 16 patients with HBsAg > 20000 IU/mL at week 24 achieved a virological response at week 48.CONCLUSION: Baseline HBsAg level in combination with HBV DNA may become an effective predictor for guiding optimal therapy with PEG-IFN-α2b against HBeAg-positive CHB.

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.

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.

Prediction of the Response to Pegylated Interferon α-2a in Patients with HBeAg Positive Chronic Hepatitis B through Decline of Serum HBV DNA and Hepatitis B Virus Surface Antigen at Week 4

Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon(PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week(r = 0.8202, P < 0.0001 and r = 0.6838, P < 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week(r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week(r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.

富马酸替诺福韦酯和富马酸丙酚替诺福韦序贯联合聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者的疗效比较

目的:比较富马酸替诺福韦酯(tenofovir disoproxil fumarate,TDF)和富马酸丙酚替诺福韦(tenofovir alafenamide fumarate,TAF)两种药物序贯加用聚乙二醇干扰素α-2b在慢性乙型肝炎患者中的疗效。方法:选取慢性乙型肝炎患者160例,根据用药方案不同分成实验组和对照组各80例,分别接受TAF治疗和TDF治疗,均治疗24周后加用聚乙二醇干扰素α-2b治疗72周。观察指标包括HBV-DNA阴转率、HBeAg阴转率、HBsAg阴转率、HBsAg滴度、HBVDNA定量和ALT水平。结果:共有128例参与者完成了研究,其中实验组62例,对照组66例。96周时,实验组的HBsAg转化率、HBsAg滴度和HBVDNA定量明显优于对照组,差异有统计学意义(P<0.05)。实验组的HBVDNA清除率和e抗原转化率也高于对照组,但差异接近显著(P=0.058和P=0.085)。实验组的ALT值在72周和96周时均低于对照组,差异有统计学意义(P<0.05)。结论:TAF联合长效干扰素治疗慢性乙型肝炎疗效明显优于TDF联合长效干扰素,可以有效改善患者的病毒学指标和肝功能,是一种更为有效的治疗方案。

Combination of pegylated interferon and lamivudine for patients with chronic hepatitis B who have failed treatment

BACKGROUND: Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efficacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment. METHODS: Twenty patients with CHB proven by liver biopsy, with ALT levels >1.5×ULN,HBV DNA levels>141 500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5μg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was defined as normalization of ALT and DNA response as HBV DNA<141 500 copies/ml. Secondary efficacy measures included HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive patients). RESULTS: Twenty patients were treated, of whom 16 were HBeAg positive. At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg), HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients. At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed, with normal ALT only in 2 (10%) (1 of 16 HBeAg+ and 1 of 4 HBeAg-), and all 5 patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg-positive patients. None of the patients lost HBsAg. CONCLUSIONS: The combination of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB patients with a failed treatment. New treatment strategies need to be developed.

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: a randomized trial

AIM: To investigate the efficacy of pegylated interferon alfa(PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus(HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily(n = 21) or PEG-IFNα alone(n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed.RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9(43%) patients receiving combination therapy and 12(63%) patients receiving PEG-IFNα alone(P = 0.199). Decline in hepatitis B surface antigen(HBs Ag) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients(38%) receiving combination therapy and 10 patients(53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7(33%) and 8(42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBs Ag and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance.CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.

Pegylated IFN-α2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

AIM: To investigate the role of pegylated-interferon (IFN)α-2b in the management of patients with lamivudine-resistant chronic hepatitis B. METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFNα-2b (100μg sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS: Nine patients (45%) had a partial viro-logical end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n = 5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION: Pegylated IFNα-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.

Liver Histopathological Features Influencing HBeAg Seroconversion in Patients with HBeAg-positive Chronic Hepatitis B Treated with Pegylated Interferon α

Objective To investigate the efficiency of pegylated interferon α therapy for patients with HBe Ag-positive chronic hepatitis B(CHB) and explore whether liver histopathological features and other factors might influence HBe Ag seroconversion.Methods Total of 80 HBe Ag-positive CHB patients who received liver puncture were treated with pegylated interferon α once a week for 48 weeks. The rate of HBe Ag seroconversion was determined after therapy, and the factors influencing HBe Ag seroconversion were analyzed.Results The rate of HBe Ag seroconversion was 30.00% at the end of treatment. The rate of HBe Ag seroconversion gradually increased with the elevation of liver inflammatory activity(χ2 = 9.170, P = 0.027). But liver fibrosis has little correlation with the rate of HBeA g seroconversion(χ2 = 5.917, P = 0.116). Except HBeA g, other baseline indexes including gender, age, serum ALT and serum HBV DNA 1evels had no statistical difference between the patients with HBe Ag seroconversion and the patients without HBe Ag seroconversion. By binary logistic regression analysis, liver inflammation and HBeA g were influencing factors for HBeA g seroconversion. Conclusions Pegylated interferon α therapy induces a higher rate of HBeA g seroconversion in HBeA g-positive chronic hepatitis B patients with severe liver inflammation, so the liver biopsies should be performed in time.

弥漫大B细胞淋巴瘤患者血浆IFN-γ、IL-2及外周血T淋巴细胞亚群、NK细胞与其临床分期的关系

目的探讨弥漫大B细胞淋巴瘤(DLBCL)患者血浆干扰素γ(IFN-γ)、白细胞介素-2(IL-2)水平及外周血T淋巴细胞亚群、自然杀伤(NK)细胞与临床分期的关系。方法纳入河南中医药大学第三附属医院2020年12月至2022年12月收治的DLBCL患者198例,根据临床分期分成Ⅰ期组(31例)、Ⅱ期组(56例)、Ⅲ期组(59例)、Ⅳ期组(52例)。比较4组血浆IFN-γ、IL-2及外周血CD3^(+)、CD3^(+)CD4^(+)T、CD3^(+)CD8^(+)T、NK细胞水平,分析各指标与DLBCL分期的相关性。结果Ⅲ期组、Ⅳ期组的血浆IFN-γ、IL-2水平低于Ⅰ期组、Ⅱ期组(P<0.05)。Ⅲ期组、Ⅳ期组外周血CD3^(+)、CD3^(+)CD4^(+)T、CD3^(+)CD8^(+)T、NK细胞水平低于Ⅰ期组、Ⅱ期组(P<0.05)。DLBCL患者IFN-γ、IL-2与CD3^(+)、CD3^(+)CD4^(+)T、CD3^(+)CD8^(+)T、NK细胞水平呈正相关(P<0.05)。DLBCL患者的血浆IFN-γ、IL-2及外周血CD3^(+)、CD3^(+)CD4^(+)T、CD3^(+)CD8^(+)T、NK细胞水平与临床分期呈负相关(P<0.05)。IFN-γ、IL-2、CD3^(+)、CD3^(+)CD4^(+)T、CD3^(+)CD8^(+)T、NK细胞水平增高是控制临床分期增高的保护因素(P<0.05)。结论DLBCL患者的临床分期与血浆IFN-γ、IL-2及外周血T淋巴细胞亚群、NK细胞水平相关,且血浆IFN-γ、IL-2水平与T淋巴细胞亚群、NK细胞存在相关性,上述指标有望对DLBCL进展风险进行预测。

聚乙二醇干扰素α-2b治疗HBeAg阴性慢性乙型肝炎实现临床治愈的预测因素分析

目的探究聚乙二醇干扰素α-2b(PEG-IFNα-2b)治疗HBeAg阴性慢性乙型肝炎[HBeAg(-)CHB]患者实现临床治愈的预测因素。方法回顾性研究2016年8月―2020年12月泰州市人民医院收治的PEG-IFNα-2b治疗的HBeAg(-)CHB患者,分为治愈组和未治愈组。单因素分析、logistic多因素分析筛选出临床治愈的预测因素,ROC-AUC评价预测效能。根据ROC-AUC得出的预测因素的截断值分别进行分组,采用Kaplan-Meier生存曲线估算HBsAg累积清除率,Log-rank对数秩检验用于比较组间差异。结果共有116例HBeAg(-)CHB患者入组,随访时间124.93(109.61~140.11)周,临床治愈率为31.03%(36/116)。单因素分析得出有统计学意义的指标:基线HBsAg水平(Z=-6.283,P<0.001)、基线肝硬化患者的比例(χ^(2)=8.344,P=0.004)、12周和24周HBsAg下降幅度(Z=-3.922、-5.144,P均<0.001)、疗程中ALT一过性升高的峰值(Z=-6.081,P<0.001)。多因素分析提示基线HBsAg水平(P=0.001)、治疗24周HBsAg下降幅度(P=0.001)以及疗程中ALT一过性升高的峰值(P=0.019)与临床治愈独立相关。上述三个因素的截断值分别为1.68 lg IU/mL、1.28 lg IU/mL和110.50 U/L,三个因素单独及联合预测临床治愈的AUC分别为0.802、0.855、0.833和0.963。比较基线HBsAg≤1.68 lg IU/mL组和>1.68 lg IU/mL组、24周HBsAg下降幅度≥1.28 lg IU/mL组和<1.28 lg IU/mL组、疗程中ALT一过性升高的峰值≥110.50 U/L组和<110.50 U/L组组间的HBsAg累积清除率,差异均有统计学意义(χ^(2)=30.966、42.925、28.463,P均<0.001)。结论基线HBsAg水平越低的HBeAg(-)CHB患者,给予PEG-IFNα-2b治疗可获得更高的HBsAg清除率,动态随访中,24周HBsAg下降幅度大、ALT一过性升高峰值大的患者,临床治愈率更高。

HBeAg阳性CHB患者血清白介素-8与聚乙二醇化干扰素-α治疗的关系

目的:探讨血清白介素-8(IL-8)能否作为预测因子评估HBeAg阳性慢性乙型肝炎(CHB)患者接受聚乙二醇化干扰素-α(PEG-IFN-α)抗病毒治疗的疗效。方法:通过接受PEG-IFN-α抗病毒治疗48周的53例HBeAg阳性CHB患者,分析比较非持续应答患者和持续应答患者血清IL-8基线和治疗48周时含量差异,并分析患者血清IL-8基线与临床特征的相关性。采用受试者工作特征曲线(ROC)评估血清IL-8基线含量在预测PEG-IFN-α抗病毒疗效的临床价值。结果:与非持续应答患者血清IL-8含量(181.68±84.43)pg/mL相比较,持续应答患者血清IL-8基线含量(124.81±74.12)pg/mL显著降低。经48周PEG-IFN-α抗病毒治疗后,持续应答患者血清IL-8含量也显著降低,而非持续应答患者血清IL-8含量变化不显著。非持续应答患者和持续应答患者的血清IL-8基线含量均与HBsAg、HBeAg和HBV-DNA呈正相关,但相关性强弱有差异。血清IL-8基线含量预测HBeAg阳性CHB患者接受PEG-IFN-α治疗的持续应答的曲线下面积为0.711。结论:血清IL-8基线含量高低影响PEGIFN-α治疗HBeAg阳性CHB患者的抗病毒疗效,是潜在的临床预测指标。

聚乙二醇干扰素α-2b治疗HBeAg阴性慢性乙型肝炎患者实现HBsAg清除的预测因素及列线图构建

目的 利用血清学指标,基于LASSO回归建立HBe Ag阴性的慢性乙型肝炎(CHB)患者在接受聚乙二醇干扰素α-2b(PEG-IFNα-2b)治疗后实现HBs Ag清除的早期预测模型,并评估模型的预测价值。方法 选取2020年4月—2021年10月在徐州医科大学附属医院接受PEG-IFNα-2b治疗的136例HBe Ag阴性CHB患者,其中47例为PEG-IFNα-2b初次治疗患者(初始治疗),89例为经核苷(酸)类似物治疗48周后接受PEG-IFNα-2b治疗患者(经治治疗)。将患者按照7∶3的比例随机分为训练集(95例)和验证集(41例),收集训练集和验证集患者基线和治疗12周时的病毒学指标、血常规和肝功能等指标的检测结果。以治疗48周时患者HBs Ag状态为变量,将患者分为阴转组(38例)和未阴转组(98例)。符合正态分布的计量资料两组间比较采用成组t检验,不符合正态分布的计量资料两组间比较采用Wilcoxon秩和检验。分类变量两组间比较采用χ^(2)检验。采用LASSO回归、单因素和多因素Logistic回归分析构建列线图模型,并利用ROC曲线分析评估其预测能力,根据ROC曲线下面积(AUC)比较预测价值。结果 在训练集中,95例HBeAg阴性CHB患者经过PEG-IFNα-2b治疗48周后,HBsAg阴转组有27例,未阴转组有68例。根据单因素Logistic回归结果,以P<0.2为筛选条件,将性别、基线HBV DNA水平、0~12周HBV DNA下降水平、基线HBsAg水平、0~12周HBsAg下降水平、基线AST水平、0~12周AST下降水平、基线ALT水平和0~12周ALT下降水平,共9个指标纳入LASSO回归。根据LASSO回归结果,性别、基线HBsAg水平、0~12周HBsAg下降水平和0~12周ALT下降水平是非零变量,纳入多因素logistic回归。根据多因素Logistic回归分析结果,筛选出4个独立预测因素,分别是性别(OR=5.38,95%CI:1.11~34.21,P=0.049)、基线HBsAg水平(OR=0.12,95%CI:0.04~0.26,P<0.001)、0~12周HBsAg下降水平(OR=5.54,95%CI:1.97~19.18,P=0.003)、0~12周ALT下降水平(OR=0.99,95%CI:0.97~1.00,P=0.039)。最终,基于多因素Logistic回归结果,构建列线图模型,并通过ROC曲线分析列线图模型的预测价值。在训练集中,列线图模型的AUC为0.934(95%CI:0.886~0.981)。在验证集中,列线图模型的AUC为0.921(95%CI:0.838~1.000)。同时,校准曲线和决策曲线结果表明模型具有较好一致性和精准度。结论 根据患者基本信息和血清学指标,基于LASSO回归,利用性别、基线HBsAg水平、0~12周HBsAg下降水平和0~12周ALT下降水平构建了列线图,可以预测PEG-IFNα-2b治疗HBeAg阴性CHB患者实现HBsAg清除的概率,可为患者的临床治疗提供重要的参考。

Effects of recombinant human interferon α 2b atomization on serum cytokines and peripheral blood immune cells in children with HFMD

Objective:To study the effects of recombinant human interferon 2b atomization on serum cytokines and peripheral blood immune cells in children with HFMD.Methods: Children who were diagnosed with hand-foot-and-mouth disease in Tongji Hospital? Tongji Medical College Huazhong University of Science & Technology between June 2014 and August 2017 were selected as the research subjects and randomly divided into the interferonα2b group who accepted human recombinant interferonα2b atomization combined with conventional symptomatic treatment and the control group who accepted conventional symptomatic treatment. The contents of cytokines in serum and the contents of immune cells in peripheral blood were determined before treatment as well as 3 days and 5 days after treatment. Results: 3 days and 5 days after treatment, IL-6, IL-13, TNF-α, CRP, MCP-1, VCAM-1 and ICAM-1 contents in serum as well as CD19+CD24highCD27+B cell contents in peripheral blood of both groups of children were greatly lower than those before treatment whereas CD3+CD4+T cell, CD3+CD8+T cell and CD16+CD56+NK cell contents in peripheral blood were higher than those before treatment, and IL-6, IL-13, TNF-α, CRP, MCP-1, VCAM-1 and ICAM-1 contents in serum as well as CD19+CD24highCD27+B cell contents in peripheral blood of interferonα2b group were significantly lower than those of control group whereas CD3+CD4+T cell, CD3+CD8+T cell and CD16+CD56+NK cell contents in peripheral blood were higher than those of control group.Conclusion: Recombinant human interferonα2b atomization treatment of HFMD can reduce the inflammatory response and improve the immune response.