Immunogenicity of recombinant hepatitis B vaccine in treatment-nave and treatment-experienced chronic hepatitis C patients: The effect of pegylated interferon plus ribavirin treatment

AIM： To retrospectively evaluate the vaccinationinduced anti-HBs seroconversion rates in treatmentnaive and treatment-experienced chronic hepatitis C （CHC） patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon （PEG） plus ribavirin （RIB） treatment. METHODS： Seventy treatment-naive CHC patients （group A）, 22 sustained virological responders-SVR following interferon （IFN） plus RIB treatment CHC patients （group B） and 121 healthy subjects （group C） had been participated in the same HBV vaccination schedule （20 μg, 0-1-6 mo）. Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups： Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student＇s t-test and chi-square analysis （P 〈 0.05）. RESULTS： Fifty-eight of 70 group A patients （82.85%）, 20/22 group B （90.9%） and 112/121 healthy subjects （92.56%） had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients （P = 0.04）. The corresponding rates were comparable between group A and group B CHC patients （P = 0.38）. The vast majority of non-responders （10/14, 71.43%） had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 （20% versus 26.7%, P = 0.67）, mo 2 （46.7% vs 60%, P = 0.46） and mo 7 （86.7% versus 93.3%, P = 0.54） of follow-up. CONCLUSION： The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

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.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.

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。

Boceprevir or telaprevir in hepatitis C virus chronic infection:The Italian real life experience

AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.

Successful interferon desensitization in a patient with chronic hepatitis C infection

Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.

Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: A prospective study on patients with HCV related cirrhosis

AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive effect of IFN plusribavirin treatment are lacking.METHODS:A total of 101 patients(62 males and 39 females,mean age 55.1±1.4 years)with histologically proven HCVrelated liver cirrhosis plus compatible biochemistry andultrasonography were enrolled in the study.Biochemistryand ultrasonography were performed every 6 mo.Ultrasoundguided liver biopsy was performed on all detected focallesions.Follow-up lasted for 5 years.Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytesnuclei,was expressed as AgNOR-Proliferative index(AgNOR-PI)(cut-off=2.5).Forty-one patients(27 males,14 females)were only followed up after the end of anyearly treatment with IFN-alpha2b(old treatment controlgroup=OTCG).Sixty naive patients were stratified accordingto sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b+ribavirin(treatmentgroup=TG),the remaining were not treated(control group=CG).Nonresponders(NR)or relapsers in the TG receivedfurther IFN/ribavirin treatments after a 6 mo of withdrawal.RESULTS:AgNOR-PI was significantly lowered by IFN(P<0.001).HCC incidence was higher in patients withAgNOR-PI>2.5(26% vs3%,P<0.01).Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCCduring follow-up.The Kaplan-Mayer survival curves showedstatistically significant differences both between OTCG andCG(P<0.004)and between TG and CG(P<0.003).CONCLUSION:IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best resultsin terms of HCC prevention.AgNOR-PI is a useful markerof possible HCC development.

Update on hepatitis B virus infection

Chronic infection with hepatitis B virus (HBV) leads to the development of hepatocellular carcinoma and/or chronic liver failure. Despite extensive research, the immunopathogenesis is not completely understood. Viral persistence and clinical outcomes following HBV infection depend on viral factors and host factors; including genetic factors that determine a host&#x02019;s immune mechanisms. The primary goal of chronic hepatitis B (CHB) treatment is to eradicate HBV or to at least maintain suppression of HBV replication. Despite recent advances in anti-viral agents for chronic HBV infection, complete eradication of the virus has been difficult to achieve. Agents for the treatment of CHB are divided mainly into two groups: immunomodulating agents and antiviral nucleos(t)ide analogues (NAs). Although NAs are safe, effective and easily administered orally, their long-term use poses the risk of drug resistance. Currently, international evidence-based guidelines have been developed to support physicians in managing CHB patients. However, treatment of patients with drug resistance is still challenging, as only a few classes of anti-HBV drugs are available and cross-resistance between drugs can occur. In addition, as the currently available genotypic test for detection of drug resistance still has limitations in identifying the different substitutions present in the same viral genome, the development of a new virologic test to overcome this limitation is necessary. Among the predictive factors associated with response to pegylated interferon (PEG-IFN) therapy, hepatitis B surface antigen quantification is considered to be a surrogate marker for monitoring response to PEG-IFN. Current practice guidelines stress the importance of profound and durable HBV viral suppression in the treatment of CHB patients. To this end, it is essential to choose a potent antiviral drug with a low risk of resistance for initial treatment of CHB to achieve sustained virological response. This review highlights recent advances in the understanding of the immunopathogenesis of HBV and currently available and developing treatment strategies against HBV infection.

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-α) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV(50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=-0.05).CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy.Response rate of SENV to the combination therapy depends on SENV DNA level.

聚乙二醇干扰素联合富马酸替诺福韦治疗HBeAg阴性慢性乙型肝炎的临床研究

目的探讨应用聚乙二醇干扰素联合富马酸替诺福韦治疗乙肝e抗原(hepatitis B e antigen,HbeAg)阴性慢性乙型肝炎,对肝功能指标的影响。方法选取2021年1月—2022年1月来齐齐哈尔市第七医院就诊的HBeAg阴性的慢性乙型肝炎患者60例,根据随机数表法分成3组,A组为单用富马酸替诺福韦治疗乙型肝炎,B组为单用聚乙二醇干扰素治疗乙型肝炎,C组为富马酸替诺福韦联合聚乙二醇干扰素乙型肝炎,观察聚乙二醇干扰素联合富马酸替诺福韦治疗慢性乙型肝炎的临床效果。结果治疗12个月后,3组患者的谷草转氨酶(aspartate aminotransferase,AST)和谷丙转氨酶(alanine aminotransferase,ALT)水平比较,C组改善明显优于B组、A组,差异有统计学意义(P<0.05)。治疗12个月后,3组患者生化指标比较,C组患者的乙肝病毒(HBV)DNA转阴率、乙肝e抗原(HbeAg)转阴率和ALT复常率均显著高于A组及B组(70.00%、75.00%、85.00%vs 30.00%、35.00%、40.00%vs 40.00%、30.00%、45.00%),差异有统计学意义(χ^(2)=6.964,9.777,9.910,P<0.05)。结论应用聚乙二醇干扰素同时配伍富马酸替诺福韦药物对HBeAg阴性慢性乙型肝炎临床疗效十分显著,药物对患者的稳定和安全性极高,值得临床广泛推广应用。

干扰素治疗HBeAg阳性慢性乙型肝炎疗效再评价

目的 再评价干扰素（IFN）治疗HBeAg阳性慢性乙型肝炎（CHB）患者的疗效,探索预测其疗效的相关因素.方法 严格按入选标准选择HBeAg阳性CHB患者,以常规IFN 500～600万单位治疗,据随访结果及患者依从性、药物不良反应等确定疗程和调整治疗方案.结果 完成疗程者206例,128例（62.1%）在治疗结束前达到了eAg-eAb血清学转换.其中16～25岁者优于26～35岁者,非母婴垂直传播者优于可疑母婴垂直传播者;谷丙转氨酶（ALT）在治疗前5～10倍正常值上限（ULN）者,治疗早期（前3个月）较基线升高大于或等于5倍者,治疗6个月降至正常者对IFN反应更好;HBV-DNA定量在治疗前低水平者,治疗早期（前3个月）下降大于2个对数级者有更高的eAg-eAb血清学转换率.结论 ALT、HBV-DNA在治疗前的水平及治疗中的变化对IFN疗效有较好预测作用.

慢性乙肝病毒携带者抗病毒治疗有效性与安全性研究现状

目的:通过检索国内外数据库,对慢性乙型肝炎病毒携带者(chronic hepatitis B virus carriers,CHBVC)抗病毒治疗的有效性与安全性进行系统评价。方法:采用计算机检索PubMed、Embase、Cochrane Library、Web of Science、知网、万方、维普和中国生物医学文献数据库,筛选关于CHBVC抗病毒治疗核苷类似物(nucleoside analogue,NA)单用方案,α干扰素(interferon alpha,IFNα)单用方案及NA+IFNα联合方案的临床随机对照研究或队列研究文献,并使用Stata17进行Meta分析。结果:共纳入28篇文献,涉及1623例CHBVC患者接受抗病毒治疗。有效性分析:HBsAg血清清除率为20%(338/1421),其中HBeAg阴性组HBsAg清除率高达52.9%,阳性组仅为1.5%;HBeAg阴性组中HBV DNA<2000 IU/mL组的HBsAg清除率为45.6%,HBV DNA<20 IU/mL组的HBsAg清除率可达59.9%。HBsAg血清转化率为15.3%(196/946),其中HBeAg阴性组HBsAg转化率较高(38.2%),阳性组未见明显变化;HBeAg阴性组中HBV DNA<2000 IU/mL组的HBsAg转化率为34.5%,而HBV DNA<20 IU/mL组的HBsAg血清转化率可达49.4%。HBeAg血清阴转率为6.6%(34/465),随着治疗时间延长呈逐渐上升趋势,在192周时可达8.8%。HBeAg血清转化率为8%(63/700),在96周时最高(24%),同时NA+IFNα联合方案比NA单用更具优势(8.1%vs.5.4%)。HBV DNA血清阴转率总体达到70.1%(500/738)。安全性分析:共有494例患者被纳入8篇文献进行不良事件发生情况统计,总体不良事件发生率约为5.4%(28/494)。结论:CHBVC抗病毒治疗有较高的有效性和安全性,NA+IFNα联合方案及长期治疗方案对改善CHBVC效益更为明显。

联合治疗策略在应答不佳/耐药HBeAg阳性慢性乙型肝炎患者中的临床研究

目的比较采用聚乙二醇干扰素(pegylated interferon,Peg-IFN)+核苷(酸)类似物[nucleos(t)ide analogues,NAs]和NAs+NAs二种方案治疗NAs治疗应答不佳/耐药的HBe Ag阳性慢性乙型肝炎(chronic hepatitis B,CHB)的疗效和安全性,探求具有停药终点的优化治疗方案。方法选择NAs抗病毒治疗应答不佳/耐药的HBe Ag阳性CHB患者110例,根据既往NAs用药史、耐药检测结果及个人意愿,采用Peg-IFN+NAs(IFN组)或NAs+NAs(NA组)进行抗病毒治疗。比较2组在治疗48周和96周时完全病毒学应答(HBV DNA<20 IU/ml)率、HBe Ag血清学转换率及HBs Ag清除/血清学转换率。结果 IFN组58例,NA组52例,2组分别有45例和42例完成96周疗程。在治疗48周IFN组和NA组完全病毒学应答率分别为96.55%(56/58)和67.31%(35/52);96周分别为100%(45/45)和71.43%(30/42),IFN组均高于NA组(P值均为0.001)。IFN组在治疗48周和96周HBe Ag血清学转换率(20.69%、46.67%)高于NA组(5.77%、21.43%),差异有统计学意义(P=0.023、0.013)。24、48、96周时IFN组HBs Ag水平明显低于NA组。截至96周IFN组8例(17.78%)HBs Ag清除,其中3例(6.67%)发生HBs Ag血清学转换。NA组在治疗96周出现1例(2.38%)HBs Ag清除。IFN组的HBs Ag清除率高于NA组(P=0.045)。结论对于NAs治疗应答不佳/耐药的CHB患者,采用Peg-IFN+NAs和NAs+NAs的治疗方案均可有效抑制病毒复制;在HBe Ag血清学转换及HBs Ag清除方面,Peg-IFN+NAs联合治疗方案更具优势。采用以IFN为基础的联合治疗可使NAs应答不佳/耐药患者获得可靠的停药终点。

HBeAg阳性慢性乙型肝炎的抗病毒治疗研究进展

慢性乙型肝炎(CHB)已成为全球最关注的疾病之一,每年导致约100万人死于慢性乙型肝炎相关的肝硬化和肝细胞癌,抗病毒则成为慢性乙型肝炎治疗的关键。对于CHB患者,抗病毒治疗首先要实现对HBV的免疫学控制,进而阻止疾病的的进展。对于HBeAg阳性患者CHB患者,获得HBeAg血清学转换意味着达到免疫控制。近年来,干扰素(IFN)、核苷(酸)类似物(NUC)的抗病毒疗效已得到全球公认,同时不可避免地尤其是HBeAg阳性慢性乙型病毒感染患者,可能存在一些治疗过早或过于积极的问题。正确评估HBe Ag阳性慢性乙型病毒感染的疾病阶段,选择最佳治疗时期,最好地运用这些药物,单独或联合或序贯治疗,最大程度地发挥它们的作用,从而保证高效、持久的应答,仍是值得关注与探讨的话题。

干扰素α-2b与拉米夫定治疗慢性乙型肝炎的成本-效果分析

目的 :评价应用干扰素α -2b与拉米夫定治疗慢性乙型肝炎的疗效、不良反应及成本 -效果。方法 :运用药物经济学成本 -效果分析方法 ,对干扰素α -2b与拉米夫定治疗慢性乙型肝炎的疗效及成本进行比较。结果 :干扰素α -2b与拉米夫定治疗慢性乙型肝炎总有效率基本相同 ,分别为58 00 %、62 00 % (P>0 05) ;成本 -效果比分别为762 49、111 85(P<0 01)。结论 :干扰素α -2b与拉米夫定均能有效治疗慢性乙型肝炎 ,但拉米夫定成本 -效果比优于干扰素α -2b。

聚乙二醇干扰素联合利巴韦林治疗对基因1b型慢性丙型肝炎患者预存耐药相关替代的差异性分析

目的探索聚乙二醇干扰素-α(PEG interferonα,PEG IFN-α)联合利巴韦林(ribavirin,RBV)治疗对基因1b型慢性丙型肝炎(chronic hepatitis C,CHC)患者直接抗病毒药物(directly acting antiviral,DAA)的预存耐药相关替代(resistance-associated substitutions,RAS)的影响。方法选取2010年7月至2015年11月首都医科大学附属北京佑安医院收治的310例基因1b型CHC患者,均予以PR方案,依据是否获得持续病毒学应答(sustained virology response,SVR)分为SVR组与非SVR组。提取患者基线以及治疗失败时的HCV RNA,聚合酶链反应(polymerase chain reaction,PCR)扩增并测序HCV NS3/4A、NS5A、NS5B区基因,进行DAA相关RAS差异性比较。结果SVR组184例,非SVR组126例。基线NS3/4A区82.5%存在DAA相关RAS,S122为38.8%,Q80L为0.7%;基线NS5A区44.5%检测到RAS,Y93H为6.3%,L31M为2.9%;基线NS5B区88.3%检测到RAS,S282为0.7%,L159F为5.0%。SVR组与非SVR组基线RAS发生率的差异均无统计学意义(P>0.05)。PR治疗失败后部分患者关键位点RAS,如L31M、Y93H出现增加,但差异无统计学意义,π检验以及Tajima’s D检测均未观察到特殊的进化模式。结论基因1b型CHC患者中存在DAA相关RAS,这些突变大多为低度耐药突变,其对PR治疗疗效无影响,且未观察到IFN的选择压力对RAS的变化造成影响。

阿德福韦酯联合干扰素治疗HBeAg阳性慢性乙型肝炎成本-疗效分析

目的评价阿德福韦酯联合干扰素治疗HBeAg阳性慢性乙型肝炎所产生的经济效果。方法对本院收治的89例HBeAg阳性慢性乙型肝炎分成2种药物治疗方案,即联合用药组(阿德福韦酯+干扰素)、单用药组(阿德福韦酯)。应用药物经济学观点进行成本-效果比较分析。结果联合用药组和单用药组治疗总有效率为74.47%和42.86%,药品成本-疗效(C/E)为23.14和31.50。结论阿德福韦酯联合干扰素治疗慢性乙型肝炎效果良好,成本-疗效较低,值得在临床上推广。

IFN-α、胸腺肽联合利巴韦林治疗抗-HBe阳性的慢性乙型肝炎疗效观察

探讨IFN-α、胸腺肽联合利巴韦林治疗抗-HBe阳性的慢性乙型肝炎疗效。抗-HBe阳性的慢性乙型肝炎72例,随机分为两组,A组为治疗组,使用α-1b干扰素(赛若金)、胸腺肽和利巴韦林治疗。B组为对照组,给α-1b干扰素(赛若金)和胸腺肽治疗。A组治疗12个月,随访6个月、12个月时肝功能复常率及HBV-DNA转阴率分别是72.2％、75％;61.1％、63.9％和55.6％、58.3％,效果显著。与对照组相比,HBV-DNA阴转率存在显著性差异;肝功能复常率在治疗结束时无显著差异,随访12个月时差异显著。IFN-α、胸腺肽联合利巴韦林治疗抗-HBe阳性的慢性乙型肝炎疗效显著,副反应低,值得进一步研究和应用。