Clinical effects of pegylated interferon alfa-2b combined with nucleotide analogues therapy on HBV associated liver cancer / 国际外科学杂志

Objective:To evaluate the effects of pegylated interferon (Peg-IFN) alfa-2b combined with nucleotide analogues (NAs) on the recurrence of hepatitis B-related liver cancer after resection, and to explore the changes of HBsAg and HBV DNA in patients with chronic hepatitis B liver cancer during postoperative treatment.Methods:The prospective study was conducted. Clinical data of 43 patients with hepatitis B-related liver cancer who underwent radical resection treated in 900th Hospital of People′s Liberation Army were prospectively analyzed from January 2020 to December 2021. Among 43 patients, there were 39 males and 4 females, the age was 30-76 years. According to different treatment methods they were divided into two groups, the patients treated by Peg-IFN alfa-2b combined with NAs were devided into the IFN group( n=10), and those treated by NAs alone into the NAs group( n=33). Two-pair semi-quantitative were collected every 3 months after operation. The recurrence-free survival rate, recurrence time after 2 years in the two groups, the clearance rate and the negative rate of HBsAg and HBV DNA in the two groups. Peg-IFN alfa-2b was evaluated in improving the prognosis of hepatitis B-related liver cancer. The measurement data of normal distribution were expressed by mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Chi-square test was used for comparison between the two groups of count data. Repeated analysis of measurement variance was used for analysis HBsAg and HBV DNA changes of the interferon group overall survival time and recurrence-free surrival time of patients was estimated using Kaplan-Meier method and the difference between groups was assessed using Log-rank test. Results:HBsAg and HBV DNA: The HBsAg clearance rate at 24 weeks and that at 48 weeks in the IFN group were 24.6% and 59.0% respectively. The HBsAg negative rate at 48 weeks was 16.7%. The HBV DNA clearance rate at 24 weeks and that at 48 weeks were 33.9% and 53.8% respectively. The HBV DNA negative rate was 0 at 48 weeks. The levels of HBsAg and HBV DNA in the IFN group decreased gradually with time. There were statistically differences between the levels of HBsAg and HBV DNA at 0 weeks, 24 weeks and 48 weeks( P<0.05). The 2-year overall survival rates of IFN group and NAs group were 100% and 90.9% respectively. The 2-year recurrence-free survival rates were 90.0% and 63.6% respectively. There were no significant statistical differences in the overall survival rate and recurrence-free survival rate between the groups ( P>0.05). The postoperative recurrence time of the IFN group and the NAs group were (15.00±7.07) months and (5.78±3.39) months respectively. The difference between the two groups was statistically significant ( t=3.160, P<0.01). Conclusion:Long-term antiviral therapy of Peg-IFN alfa-2b combined with NAs can prolong the recurrence time of liver cancer, reduce the levels of HBsAg and HBV DNA in serum, and potentially improve the survival rate of the patients compared with therapy of NAs alone.

Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts / 器官移植

Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.

Predictors of HBsAg clearance in HBeAg-negative chronic hepatitis B patients treated with pegylated interferon α-2b and the construction of a nomogram model / 临床肝胆病杂志

ObjectiveTo establish an early predictive model using serological markers based on LASSO regression for predicting the possibility of HBsAg clearance in HBeAg-negative chronic hepatitis B （CHB） patients treated with pegylated interferon α-2b （PEG-IFNα-2b）， and to investigate the diagnostic value of the model. MethodsA total of 136 HBeAg-negative CHB patients who received PEG-IFNα-2b treatment in the Affiliated Hospital of Xuzhou Medical University from April 2020 to October 2021 were enrolled， among whom 47 received PEG-IFNα-2b for the first time （previously untreated） and 89 received PEG-IFNα-2b after 48 weeks of treatment with nucleos（t）ide analogues （treatment-experienced）. The patients were randomly assigned to a training set with 95 patients and a validation set with 41 patients at a ratio of 7∶3， and related data were collected for both groups， including virological markers， routine blood test results， and liver function at baseline and week 12 of treatment. According to HBsAg status at week 48 of treatment， the patients were divided into seroconversion group with 38 patients and non-seroconversion group with 98 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical variables between two groups. The LASSO regression analysis and univariate and multivariate logistic regression analyses were used to establish a nomogram model； the receiver operating characteristic （ROC） curve was used to assess its predictive ability， and the area under the ROC curve （AUC） was used for comparison of predictive value. ResultsIn the training set， 95 HBeAg-negative CHB patients were treated with PEG-IFNα-2b for 48 weeks， among whom there were 27 patients in the seroconversion group and 68 in the non-seroconversion group. The univariate Logistic regression analysis， with P<0.2 as the criterion for screening， showed that 9 indicators were included in the LASSO regression analysis， i.e.， sex， baseline HBV DNA level， the reduction in HBV DNA in 0 — 12 weeks， baseline HBsAg level， the reduction in HBsAg in 0 — 12 weeks， baseline aspartate aminotransferase （AST） level， the reduction in AST in 0 — 12 weeks， baseline alanine aminotransferase （ALT） level， and the reduction in ALT in 0 — 12 weeks. The LASSO regression analysis showed that sex， baseline HBsAg level， the reduction in HBsAg in 0 — 12 weeks， and the reduction in ALT in 0 — 12 weeks were non-zero variables and were included in the multivariate Logistic regression analysis. The multivariate Logistic regression analysis obtained 4 independent predictive factors， i.e.， sex （odds ratio ［OR］=5.38， 95% confidence interval ［CI］： 1.11 — 34.21， P=0.049）， baseline HBsAg level （OR=0.12， 95%CI： 0.04 — 0.26， P<0.001）， the reduction in HBsAg in 0 — 12 weeks （OR=5.54， 95%CI： 1.97 — 19.18， P=0.003）， and the reduction in ALT in 0 — 12 weeks （OR=0.99， 95%CI： 0.97 — 1.00， P=0.039）. A nomogram model was established based on the results of the multivariate Logistic regression analysis， and the ROC curve was used to assess the predictive value of this nomogram model. This nomogram model had an AUC of 0.934 （95%CI： 0.886 — 0.981） in the training set and an AUC of 0.921 （95%CI： 0.838 — 1.000） in the validation set. In addition， the results of calibration curve and decision curve analyses showed that the model had good consistency and accuracy. ConclusionBased on general information and serological markers， the LASSO regression analysis is used to establish a nomogram model using sex， baseline HBsAg level， the reduction in HBsAg in 0 — 12 weeks， and the reduction in ALT in 0 — 12 weeks， and this model can be used to predict the probability of achieving HBsAg clearance in HBeAg-negative CHB patients treated with PEG-IFNα-2b， which provides important reference and theoretical support for the clinical treatment of patients.

Impact of HCV Genome Structure on Responder to Pegylated Interferon Therapy in Egyptian Patients

This study aimed to investigate relationship of the HCV genome structure and treatment with Pegylated Interferonα/Ribavirin (peg-IFNα/RBV) Egyptian patient. Mutations in two sites of HCV genome; the internal ribosome entry site(IRES) and the interferon sensitivity determining region (ISDR) of HCV genotype 4a were studied in details including DNAsequences and mutations detection in response to treatment. Ninety patients, responders and non-responders, to treatmentwith peg-IFN α /RBV were included in this study. IRES and ISDR regions were amplified by RT-PCR using specific designedprimers, and amplified regions were sequenced. The data obtained were aligned with published sequences in GenBank usingBLAST program. Results of this study have revealed that there are different mutations in the studied sequences in both ISDRand IRES regions. The predicted amino acids sequences in the ISDR region showed significant differences ranging from oneup to more than eight mutations in the HCV Genome sequences. Although there was a significant difference betweensequences of HCV RNA isolated from responders and non-responders, these data were not able to give an absolute answerwhether response to interferon therapy is directly/relates to the structure of the HCV genome

Changes and clinical significance of γδT cells in peripheral blood of patients with chronic hepatitis B during pegylated interferon α-2a treatment / 中华肝脏病杂志

Objective@#To observe the changes of γδT cells in the peripheral blood of patients with chronic hepatitis B (CHB) during pegylated interferon α-2a treatment, and to analyze the correlation between clinical indicators and curative effects. @*Methods@#Peripheral blood of hepatitis B e antigen (HBeAg)-positive CHB patients were collected at different time points of Peg-IFNα-2a treatment, including 17 patients at 0 weeks, 20 patients at 12 weeks, 20 patients at 24 weeks, and 16 patients at 48 weeks. From these 11 patients, blood samples were frequently observed at 0, 12, 24, and 48 weeks of treatment. The frequencies of γδT and its subpopulation cells Vδ1T, Vδ2T, effector memory γδT (γδTem), central memory γδT (γδTcm), initial γδT (γδTnaive) and terminal differentiation effect γδT (γδTeff) cells in peripheral blood were detected by flow cytometry. Liver function, serum HBV markers and HBV DNA levels were measured simultaneously. SPSS 23.0 statistical software was used to analyze the differences in cell proportions at each treatment time point, and the correlation between cell proportions and alanine aminotransferase (ALT), HBsAg, HBeAg or HBV DNA levels. In addition, the correlation between the proportions of γδT and its subpopulation cells and the response to Peg-IFNα-2a treatment in the 11 patients with continuous follow-up were analyzed. @*Results@#The percentage of γδT and Vδ2T cells in peripheral blood of patients with CHB decreased gradually during the period of 0-48 weeks of Peg-IFNα-2a treatment. The percentages of γδT cells and Vδ2T cells at 48 weeks were 6.89% (5%, 8.15%), 4.61% (2.16%, 6.50%), respectively; significantly lower than the 0 week [12.5% ​​(7.73%, 19%), 6.59% (3.86%, 13.62%)], the differences were statistically significant (P < 0.05). The proportions of Vδ1T, γδTem, γδTcm, γδTnaive, or γδTeff subpopulations were not statistically different at each time points (all P > 0.05). At the same time, the levels of ALT, HBsAg, HBeAg or HBV DNA were positively correlated with the ratio of γδT or Vδ2T cells (P < 0.05). Among the 11 patients with continuous followed- up, the proportion of γδTem cells in responders was significantly lower than that of non-responders at each time points, and the difference was statistically significant (P < 0.05). There was no statistically significant difference between the two groups (all P > 0.05). @*Conclusion@#The proportion of γδT cells in the course of CHB treatment with Peg-IFNα-2a reduces the liver inflammation by decreasing the replication of HBV virus. Chronic hepatitis B patients with a lower proportion of effector memory (γδTem) cells may be more likely to get better response with Peg-IFNα-2a.

Discussion on optimal duration of pegylated interferon α combined with ribavirin for chronic hepatitis C in HIV-infected patients / 中华肝脏病杂志

Objective@#To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients.@*Methods@#A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4+ cell counts: A1 subgroup, 79 cases, CD4+ counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4+ counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4+ counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4+ counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ 2 test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests.@*Results@#There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05).@*Conclusion@#HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4+ counts 200 cells/ μl.

Detection and clinical significance of differentially expressed microRNAs in chronic hepatitis B patients before being treated with pegylated interferon / 中华实验和临床病毒学杂志

Objective@#To detect differentially expressed microRNAs in chronic hepatitis B (CHB) before being treated with pegylated interferon (PegIFN) and the relationship between their target genes and HBsAg loss.@*Methods@#Pretreatment differentially expressed microRNAs between different response groups were screened using high throughput microarrays and validated by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Bioinformatics analysis was performed to determine their target genes potential mechanistic roles.@*Results@#A total of 417 microRNA were differentially expressed between different response groups, among which 342 were up-regulated and 75 were down-regulated. miR-3960, miR-126-3p, miR-23 a-3p and miR-335-5p were verified to be down-regulated by RT-qPCR result in HBsAg loss group. Bioinformatic analysis result show that the relevant pathways of microRNAs include AMPK signal pathway, NOD-like signal pathway, NF-kappa B signal pathway and mTOR signal pathway.@*Conclusions@#HBsAg loss is probably achieved as the result of genes expression regulated in association with immune response, further enhance the immune response of HBV elimination and acquire HBsAg loss.

HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study / 中华肝脏病杂志

Objective@#Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.@*Results@#At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.@*Conclusion@#Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Clearance of HBsAg in patients with chronic hepatitis B treated by entecavir plus Peg IFNα-2b following initial entecavir monotherapy / 中华临床感染病杂志

Objective To analyze the efficacy of entecavir (ETV) combined with Peg IFNα-2b in chronic hepatitis B ( CHB) patients with low levels HBsAg following initial ETV treatment.Methods Sixty-nine CHB outpatients achieving serum HBsAg ＜2 000 IU/mL and HBV DNA＜100 IU/mL following initial ETV treatment in Pujiang People's Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to January 2016 were enrolled.Patients were randomly assigned in two groups: 39 patients in combination group received ETV (0.5 mg/d ) and Peg IFNα-2b (1.5 μg· kg－1· week －1, hypodermic injection), and 30 patients in ETV group received ETV (0.5 mg/d) alone.Serum HBsAg quantification, negative conversion rate of HBsAg and HBeAg , and levels of aminotransferase (ALT) were measured at baseline , 12th, 24th, 48th, 72th and 96th week after treatment.Results The levels of HBsAg in the combination group decreased gradually with the prolongation of therapy , which were lower than those in ETV group 24 week after treatment (Z＝－2.566,P＜0.05),and at 48th, 72th and 96th week (Z＝－3.499,－3.825 and －3.864,P＜0.01).Clearance of HBsAg appeared in the combination group at 24th week,the clearance rates were 7.70%(3/39) and 28.20%(11/39) at 24th and 96th week, respectively;while the clearance of HBsAg occurred in ETV group at 96th week, the clearance rate was only 3.30%(1/30).The negative conversion rates of HBsAg in combination group were higher than those in ETV group at 48th,72th and 96th week (P＜0.05 or＜0.01).In the combination group, there were 11 cases of clinical cure , 11 cases of clinical efficacy and 17 cases of clinical effectiveness , while there were 1, 1 and 28 cases in ETV group,respectively.The treatment effect of the combination group was better than that of ETV group(χ2＝18.496,P＜0.01).Serological conversion rates of HBeAg were 30.00%(6/20) and 65.00%(13/20) in combination group at 12th and 96th week, while those were 11.11%(2/18) and 22.22%(4/18) in ETV group at 48th and 96th week.There were significant differences in the HBeAg serological conversion rates at 12th, 24th, 72th and 96th week between two groups (P＜0.05 or ＜0.01). The levels of ALT in combination group increased at 12th and 24th week, which had significant difference compared with ETV group (Z＝－1.236 and －2.658,P＜0.05), and the ALT levels gradually declined 48 week after treatment in combination group and there were no statistical differences between two groups at other time points.The ETV combined with Peg IFNα-2b and low baseline HBeAg levels were associated with the clearance rate of HBsAg (both P＜0.01).Conclusions CHB patients with low HBsAg levels following initial ETV monotherapy can achieve high negative conversion rate of HBeAg and HBsAg with the combination treatment of ETV and Peg IFN α-2b.

Tratamiento exitoso con los nuevos antivirales de acción directa en paciente infectado con el virus de la hepatitis C con fibrosis avanzada y dos recaídas previas: Reporte de caso / Successful treatment with new direct acting antiviral in an infected patient with hepatitis C virus with advanced liver fibrosis in a treatment experienced patient: Case report

El tratamiento del virus de la hepatitis C ha presentado grandes cambios en los últimos años. El esquema base utilizado era Interferón Pegylado y Ribavirina, con el que se lograba respuesta viral sostenida (RVS) de alrededor del 50%. Con la adición de los inhibidores de proteasa Telaprevir y Boceprevir al esquema "esqueleto" de Interferon Pegylado y Ribavirina, la tasa de RVS mejoró hasta valores cercanos a 70%; sin embargo, ocurren efectos colaterales importantes y difícil adherencia. Los nuevos antivirales de acción directa (AAD) (inhibidores de la polimerasa NS5A y NS5B), tienen altas tasas de RVS alcanzando valores mayores de 95% en los diferentes genotipos, en pacientes que recibieron tratamiento previo o no, incluyendo cirróticos. Se presenta el caso de un paciente que recibió dos esquemas terapéuticos previos y con fibrosis hepática avanzada que presentó RVS al ser tratado con los nuevos AAD (Sofosbuvir y Ledipasvir). (AU)

The treatment of hepatitis C virus utilized was Pegylated Interferon and Ribavirin, achieving a sustained virological response (SVR) of about 50 %. With the addition of the first-generation protease inhibitors Telaprevir and Boceprevir to the Pegylated Interferon/Ribavirin backbone the SVR rates rose up to approximately 70%, but with important side effects and a difficult adherence. The new direct acting antivirals (NS5A and NS5B polymerase inhibitors) improved SVR rates to 95 % or greater in the different genotypes, in the treatment-naive and treatment experienced patients including patients with cirrhosis. We report the case of a patient with advanced fibrotic stage, who failed to respond to 2 regimens and was subsequently treated with Ledipasvir/Sofosbuvir and achieved virogical cure. (AU)

Meta analysis on nucleo(s)tide analogues sequential/sequential combined with pegylated interferon for the therapy of HBeAg-positive chronic hepatitis B / 中国感染控制杂志

Objective To systematically evaluate the efficacy and safety of nucleo(s)tide analogues (NAs)sequen-tial/NAs sequential combined with pegylated interferon (Peg-IFN)for the treatment of HBeAg-positive chronic hepatitis B(CHB).Methods PubMed,Cochrane Library,Embase,and Chinese Medical databases (CNKI,Wan-fang and VIP)from database establishment to March 25,2017 were retrieved,randomized controlled trials of NAs sequential/sequential combined with Peg-IFN for the treatment of CHB after application of NAs to achieve virologic response were included in study,Meta analysis was performed by RevMan 5.3 software,HBeAg seroconversion rate and HBsAg negative conversion rate at the end of treatment were compared.Results Nine studies were eventu-ally included,4 were about NAs sequential Peg-IFN,5 about NAs sequential combined with Peg-IFN.At the end of treatment,compared with using NAs monotherapy for antiviral treatment,NAs sequential/sequential combined with Peg-IFN therapy can improve HBeAg seroconversion rate(31.2% vs 11.7%;OR,3.69 [95%CI ,2.43 -5.60];P < 0.01 )and HBsAg negative conversion rate(11.5% vs 0.5%;OR,9.31 [95%CI ,2.72 - 31.89];P <0.01).According to the results of subgroup analysis,HBeAg seroconversion rate in NAs sequential Peg-IFN therapy group was higher than control group (25.3% [42/166]vs 10.0% [17/170];OR,3.1 [95%CI ,1.66 -5.79];P <0.01);HBeAg seroconversion rate in NAs sequential combined with Peg-IFN therapy was higher than control group (36.8%[63/171]vs 13.5%[23/171];OR,4.24[95%CI ,2.41 -7.46];P <0.01).Sequential/se-quential combination therapy showed more adverse reaction,most of which can be tolerated or improved after symp-tomatic treatment.Conclusion For the treatment of HBeAg-positive CHB,after application of NAs to achieve viro-logic response,NAs sequential/sequential combined with Peg-IFN therapy for 48 weeks can significantly increase HBeAg seroconversion rate and HBsAg negative conversion rate.

Meta analysis on nucleo(s)tide analogues sequential/sequential combined with pegylated interferon for the therapy of HBeAg-positive chronic hepatitis B / 中国感染控制杂志

Objective To systematically evaluate the efficacy and safety of nucleo(s)tide analogues (NAs)sequen-tial/NAs sequential combined with pegylated interferon (Peg-IFN)for the treatment of HBeAg-positive chronic hepatitis B(CHB).Methods PubMed,Cochrane Library,Embase,and Chinese Medical databases (CNKI,Wan-fang and VIP)from database establishment to March 25,2017 were retrieved,randomized controlled trials of NAs sequential/sequential combined with Peg-IFN for the treatment of CHB after application of NAs to achieve virologic response were included in study,Meta analysis was performed by RevMan 5.3 software,HBeAg seroconversion rate and HBsAg negative conversion rate at the end of treatment were compared.Results Nine studies were eventu-ally included,4 were about NAs sequential Peg-IFN,5 about NAs sequential combined with Peg-IFN.At the end of treatment,compared with using NAs monotherapy for antiviral treatment,NAs sequential/sequential combined with Peg-IFN therapy can improve HBeAg seroconversion rate(31.2% vs 11.7%;OR,3.69 [95%CI ,2.43 -5.60];P < 0.01 )and HBsAg negative conversion rate(11.5% vs 0.5%;OR,9.31 [95%CI ,2.72 - 31.89];P <0.01).According to the results of subgroup analysis,HBeAg seroconversion rate in NAs sequential Peg-IFN therapy group was higher than control group (25.3% [42/166]vs 10.0% [17/170];OR,3.1 [95%CI ,1.66 -5.79];P <0.01);HBeAg seroconversion rate in NAs sequential combined with Peg-IFN therapy was higher than control group (36.8%[63/171]vs 13.5%[23/171];OR,4.24[95%CI ,2.41 -7.46];P <0.01).Sequential/se-quential combination therapy showed more adverse reaction,most of which can be tolerated or improved after symp-tomatic treatment.Conclusion For the treatment of HBeAg-positive CHB,after application of NAs to achieve viro-logic response,NAs sequential/sequential combined with Peg-IFN therapy for 48 weeks can significantly increase HBeAg seroconversion rate and HBsAg negative conversion rate.

Effect of psychological intervention on compliance of patients with hepatitis B treated with pegylated interferon alpha 2a / 中国生化药物杂志

Objective To investigate and analyze the influence of psychological intervention on the compliance of patients with hepatitis B treated with pegylated interferon alpha 2a. Methods 100 patients with hepatitis B treated in our hospital from April 2014 to October 2016 were selected and randomly divided into the control group and the experimental group, with 50 patients in each group. The experimental group and the control group patients were treated with pegylated interferon alpha 2a treatment, treatment time was 48 weeks, no other antiviral therapy. The control group was given routine care, and the experimental group was given psychological intervention on the basis of the control group. The treatment compliance of the two groups was compared and analyzed. Results After the corresponding treatment, the score of mental health in the experimental group was (9.94±2.01) points, and the score of mental health in the control group was (6.41±2.27) points. The scores of mental health in the control group were significantly lower than those in the experimental group, with statistical difference (P<0.05). Among the patients in the experimental group, three patients had poor compliance, 20 patients had good compliance, and 27 patients had good treatment compliance, and the compliance rate was 94%. Among the patients in the control group, 15 patients had poor compliance and the rate of compliance was 70%. The rate of good treatment compliance in the control group (70%) was significantly higher than that in the experimental group (94%), with statistical difference (P<0.05). Conclusion Ppsychological intervention can significantly improve the treatment compliance of pegylated interferon alpha 2a in patients with hepatitis B, and improve the quality of life of patients, so it has the clinical significance of further promotion and application.

Effects of pegylated interferon on cellular immune function in patients with chronic hepatitis C / 中国生化药物杂志

Objective To investigate the clinical effect of pegylated interferon(IFN)on chronic hepatitis C and its effect on cellular immune function.Methods A total of 92 patients with chronic hepatitis C were enrolled in our hospital from June 2013 to October 2016.They were randomly divided into study group and control group by single and double numbers(admission order),with 46 cases in each group.The control group was treated with recombinant human interferon alpha-2b on the basis of conventional treatment.The study group was treated with pegylated interferon alpha-2a on the basis of conventional treatment.Results After treatment, the rates of RVR, EVR, ETVR and SVR in the study group(52.17%, 71.74%, 76.09% and 54.35%, respectively)were significantly higher than those in the control group(34.78%, 50%, 58.70%, 39.13%, respectively), The difference was statistically significant(P<0.05).There were no significant difference in the cellular immune function index between the two groups before treatment;After treatment,the CD3+, CD4+, CD4+/CD8+ and other immune function indexes of the study group were significantly higher than those before treatment, while the results of CD8+ were significantly lower than before treatment(P<0.05);There was no significant difference in the cellular immune function in the control group compared with before, and the difference of the cellular immune function between the 2 groups after treatment was statistically significant(P<0.05).Conclusion Pegylated interferon(IFN)on the basis of routine treatment can improve the virologic response and cellular immune function in patients with chronic hepatitis C.

The clinical features and treatment outcome of chronic hepatitis C with pegylated interferon and ribavirin in routine care

Aim: To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice. Methods: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012. Results: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57.1% of patients. The predominant HCV genotype (GT) was 3 at 60.6%, second was GT1 at 36.1% and other GTs were uncommon at about 1% or less. About half of our patients have high baseline viral load (>800,000 iu/ml), 18.3% had liver cirrhosis and 22.3% had HIV co-infection. Co-morbid illness was found in 42.9%, hypertension and type 2 diabetes were the two most common. The overall sustained virological response (SVR) by intention-to-treat analysis were 54.9% (n=150/273), 41.2% (40/97) for GT1, 100% (5/5) for GT2 and 62% (101/163) for GT3. Subgroup analysis for HCV monoinfected, treatment naïve showed SVR of 49.2% (31/63) for GT1, 100% (5/5) for GT2 and 67% (69/103) for GT3. In HCV mono-infected and treatment experienced (n=29), the SVR was 28.6% (4/14) for GT1, 21.4% (69/103) for GT3. In the HIV/HCV co-infected, treatment naïve (n=56), the SVR was 28.6% (4/14) for GT1 and 64.3% (27/42) for GT3. Treatment naïve GT3 mono-infected patients had a statistically significant higher SVR compared to treatment experienced patients (P=0.001). In GT3 patients who achieved rapid virological response, the SVR was significantly higher at 85.2% (P< 0.001). The SVR for cirrhotics were low especially for GT1 at 21% (4/19) and 31% (4/13) based on all patients and treatment naïve HCV monoinfected respectively. In GT3 cirrhotics the corresponding SVR were 57.1% (16/28) and 60.9% (14/23). Premature discontinuation rate was 21.2% with the majority due to intolerable adverse events at 12.1%. Conclusions: In our routine clinical practice, the HCV patients we treated were young, predominantly of GT3 and many had difficult-to-treat clinical characteristics. The SVR of our patients were below those reported in Asian clinical trials but in keeping with some “real world” data.

PBMCs microRNA-122 level correlates with virological responses to pegylated interferon alpha therapy in patients with hepatitis C genotype 1b / 中华实验和临床病毒学杂志

Objective@#To clarify the predictive power of PBMCs miR-122, as well as other clinical factors, for response to IFNα therapy in chronic HCV infected patients.@*Methods@#A total of 40 patients chronically infected with HCV genotype 1b were enrolled. All the patients received pegylated interferon alpha (PEG-IFN α) in combination with ribavirin for 48 weeks. To perform the analyses, the patients were compared in terms of achieving sustained virological response (SVR) or not (NSVR) at 24th week after antiviral treatment.@*Results@#SVR rate was 72.5% (29/40) and NSVR rate was 27.5% (11/40). SVR group experienced significantly lower HCV viral load, total bilirubin (TBIL), alpha fetal protein (AFP), fibroscan and laminin (LN) compared with NSVR group before treatment (P<0.05). PBMCs miR-122 expression level was also lower in SVR group than that in SNVR group, although the difference was not statistically significant (P>0.05). and there was no significant change of miR-122 level from baseline to the last available measurement between SVR group and NSVR group. However, no significant association was found between baseline PBMCs miR-122 and HCV viral load, body mass index (BMI), alanine transaminase (ALT), aspartate transaminase (AST), degree of liver fibrosis, respectively.@*Conclusions@#Our result suggest that PBMCs miR-122 level is not an efficient biomarker to predict response to IFN alpha therapy in chronic HCV patients. However, baseline HCV viral load, TBIL, AFP and fibroscan may serve as predictive factors.

The efficacy and safety of antiviral treatment in inactive hepatitis B surface antigen carriers / 中华传染病杂志

Objective To evaluate the feasibility and safety profile of pegylated-interferonα-2a (Peg IFNα-2a) combined with adefovir dipivoxil (ADV) in inactive hepatitis B surface antigen (HBsAg) carriers (IHC).Methods This was a single center, prospective and open-label study.IHC were divided into therapeutic group (T, 112 subjects) and control group (C, 72 subjects) according to personal willingness.Patients with hepatitis B virus (HBV) DNA<20 IU/mL were treated with Peg IFNα-2a monotherapy, and those with HBV DNA ≥20-<2 000 IU/mL were treated with Peg IFNα-2a combined with ADV.Total therapy duration was 96 weeks.For patients who achieved HBsAg seroconversion and continued consolidation treatment for 24 weeks, the treatment duration could be less than 96 weeks.t test was used for continuous variable comparison between the two groups, while chi-square test or Fisher′s exact probability method was used for counting data analysis.The related factors affecting HBsAg clearance was analyzed by univariate or multivariate logistic regression analysis.Results A total of 194 patients were enrolled with 112 in therapeutic group and 72 in control group.The HBsAg clearance rate and seroconversion rate at week 48 in therapeutic group were 30.8% (32/104) and 26.0% (27/104), respectively.The rates at week 96 increased to 45.2% (47/104) and 38.5% (40/104), respectively.The HBsAg clearance rates at weeks 48 and 96 in control group were both 1.5% (1/68).HBsAg seroconversion was not achieved in control group.The HBsAg clearance rate in treatment group was significantly higher than that in control group (χ2=39.066, P<0.01).The quantitative HBsAg levels at baseline (OR=2.313, 95%CI: 1.258-4.251, P=0.007), week 12 (OR=3.159, 95%CI: 1.826-5.466, P<0.01) and week 24 (OR=3.347, 95%CI: 2.050-5.465, P<0.01), the decline of HBsAg at week 12 (OR=5.343, 95%CI: 2.085-13.689, P<0.01), and week 24 (OR=4.855, 95%CI: 2.380-9.902, P<0.01), and alanine transaminase (ALT) elevation at week 12 (OR=3.520, 95%CI: 1.369-9.052, P=0.009) were independent predictors for HBsAg clearance.Conclusions Peg IFNα-2a-based treatment for IHC could achieve higher HBsAg clearance rate and seroconversion rate, and has a safety profile.Decline of HBsAg at week 12 and week 24 with ALT elevation at week 12 could predict a higher HBsAg clearance rate.

The Predictive Value of Baseline HBsAg Level and Early Response for HBsAg Loss in Patients with HBeAg-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment / 生物医学与环境科学（英文）

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

Clinical efficacy of pegylated interferon α-2a and ribavirin combined with self-extracting traditional Chinese medicine in the treatment of chronic hepatitis C / 重庆医学

Objective To study the clinical efficacy of pegylated interferon α-2a(PEG-IFN α-2a) and ribavirin combined with self-extracting traditional Chinese medicine(TCM) in the treatment of chronic hepatitis C(CHC) of gan-shen yin-deficiency and damp-heat syndrome.Methods A total of 59 cases of CHC of gan-shen yin-deficiency and damp-heat syndrome confirmed in our hospital was randomly divided into control group(n=29) and combined group(n=30).The patients in both groups were treated with PEG-IFN α-2a injection and ribavirin,and then the self-extracting TCM was added on the patients in combined group.The differences of quantitative score,improvement of liver function,RNA negative rate of HCV,the levels of IL-21,IL-6 and TNF-α,clinical treatment of total efficiency and adverse reactions were compared between the two groups before and after treatment.Results After treatment,the quantitative scores of TCM symptoms(rib-side pain,soreness and weakness of waist and knees,abdominal distension,red tongue with yellowish fur,dizziness with heavy body,insomnia and dreaminess) in combined group were significantly lower than those in control group(P＜0.05),but the difference of quantitative scores of other TCM symptoms between the two groups was not statistically significant(P＞0.05);The levels of alanine aminotransferase(ALT),aspartate aminotransferase (AST) and total bilirubin(TBIL) in combined group were better than those in control group(P＜0.05) after 48 weeks of treatment,but the difference of the levels of albumin(ALB) and glutamyl transpeptidase(GGT) were norstatistically significant in both groups(P＞0.05);The RNA negative rate of HCV in combined group was significantly higher than that in control group after 36-week or 48-week treatment(P＜0.05),but there was no statistically significant difference between the two groups after 12-week or 24-week treatment and 24-week follow-up;The levels of TNF-α,IL-17,IL-23 in combined group were significantly lower than those in control group(P＜0.05) after 48 weeks of treatment;The total efficiency of combined group is better than that of control group (93.33％ vs.72.41％,P＜0.05).There was no significant difference in adverse reactions between the two groups(P＞0.05).Conclusion The application of PEG-IFN α-2a and ribavirin combined with the self-extracting TCM in the treatment of CHC can obviously ameliorate the clinical symptoms and liver function indexes,improve the RNA negative rate of HCV,reduce the levels of inflammatory factors,and improve the clinical efficacy.

Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon α-2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C Virus

BACKGROUND/AIMS: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). METHODS: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). RESULTS: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin-28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. CONCLUSIONS: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.