Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals

BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.

Serum proteins in chronic hepatitis B patients treated with peginterferon alfa-2b

AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.

Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C

We report a case of pericarditis and chronic inflam- matory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C.The patient developed moderate weakness in the lower limbs and dyspnea.He was hospitalized for congestive heart failure.An electrocardiogram showed gradual ST-segment elevation in leads V1 through V6 without coronary artery disease.A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function.Anti-DNA antibody and anti-ds DNA IgM were positive.Neu ro logical examination revealed a symmetrical predomina ntly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution.Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.

Protracted anaphylaxis developed after peginterferon α-2a administration for chronic hepatitis C

Peginterferon is a key drug used to treat chronic viral hepatitis that is known for causing various side effects.Side effects occurring immediately after administration include headache, nausea, and influenza-like symptoms, such as fever and joint pain.However, reports of anaphylactic shock are extremely rare.Here we report a patient with protracted anaphylaxis who suffered shock symptoms after peginterferon α-2a administration for chronic hepatitis C.Although the patient improved temporarily with shock treatment, symptoms of anaphylaxis recurred.As peginterferon is often administered on an outpatient basis, it is important to recognize life-threatening side effects that may develop in a protracted manner.

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.

聚乙二醇干扰素α-2a联合恩替卡韦治疗CHB的效果及对肝功能和肝纤维化的影响

目的观察聚乙二醇干扰素α-2a(PegIFNα-2a)联合恩替卡韦治疗慢性乙型肝炎(CHB)的临床效果。方法回顾性分析2013年11月-2018年1月四川省遂宁市中心医院感染科诊治CHB患者48例的临床资料,采用PegIFNα-2a联合恩替卡韦方案者纳入联合组(n=27),单用恩替卡韦进行治疗者纳入对照组(n=21)。治疗48周后,比较2组阴转率、肝功能(Child-Pugh肝功能分级)、肝纤维化指标、肝脏硬度(LSM)值、细胞免疫指标水平变化及药物不良反应发生率差异。结果治疗48周后,联合组HBV DNA转阴率明显高于对照组(66.7%vs.38.1%,χ^2=3.884,P=0.049),而2组HBsAg、HBeAg/HbeAb、HBcAb转阴率比较差异均无统计学意义(P>0.05);2组Child-Pugh肝功能分级、LSM值及血清LN、PCⅢ、HA水平均较治疗前有显著下降,且联合组明显低于同期对照组(Z/P=2.024/0.043,t/P=4.014/<0.001、2.222/0.031、2.051/0.046、2.150/0.037);2组外周血CD4^+/CD8^+、NK细胞水平均较治疗前有显著提升,且联合组明显高于同期对照组(t/P=2.971/0.005、2.319/0.025);治疗48周内,2组血小板减少、贫血、甲状腺功能异常、头痛、恶心等并发症发生率比较差异均无统计学意义(P>0.05)。结论PegIFNα-2a联合恩替卡韦应用于CHB可获得较为理想的治疗效果,对改善患者肝功能、肝纤维化及LSM值有利,为高病毒载量CHB临床治疗提供新思路。

血清铁蛋白与培干扰素α-2a治疗慢性丙型肝炎疗效的关系

目的：探讨血清铁蛋白(SF)的变化与培干扰素α-2a(Peg-IFNα-2a)治疗慢性丙型肝炎疗效的关系。方法：试验组31例慢性丙型肝炎病人,年龄(34±s 8)a,18～65 a；15例健康志愿者为对照组。试验组给予培干扰素α-2a,180μg,皮下注射,每周1次,疗程24 wk,治疗结束后随访24 wk。分别在0,12,24及48 wk检测血清ALT及HCV RNA以判断疗效。在0 wk时检测31例病人和15例健康对照者的血清铁蛋白水平。根据疗效的不同,将病人分为持续应答、复发和无应答组。以SF值等于300μg·L^(-1)为界,将病人分为高SF组(≥300μg·L^(-1))与低SF组(＜300μg·L^(-1))。结果：慢性丙型肝炎病人的SF水平显著高于健康对照者。治疗前慢性丙型肝炎病人SF与ALT水平呈正相关。治疗前持续应答组SF含量明显低于复发组及无应答组(P＜0．01)。治疗前低SF组的病人对Peg-IFNα-2a的持续应答率显著高于高SF组的病人(P＜0．05)。结论：慢性丙型肝炎病人的SF水平与肝脏损伤程度有关,治疗前高SF水平与Peg-IFNα-2a疗效差及不稳固有关。

“补肾生髓成肝”法联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎的临床研究

目的:采用随机对照试验(RCT)方法,对比观察"补肾生髓成肝"法联合聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎(CHB)的临床疗效。方法:将80例HBeAg阳性CHB患者,随机分为治疗组和对照组,每组各40例。治疗组患者采用"补肾生髓成肝"法联合派罗欣治疗,对照组患者只采用派罗欣。治疗后第1、4、8、12、24、48、72周时检测患者外周血白细胞计数、丙氨酸氨基转移酶(ALT)、血清总胆红素(TBil)、HBV DNA、HBsAg、HBeAg、HBeAb等指标。结果:治疗组患者外周血白细胞计数在治疗后第8周为(3.74±0.49)×109/L、12周为(4.06±0.17)×109/L、24周为(4.20±0.63)×109/L,分别显著高于同期对照组的(3.49±0.58)×109/L、(3.02±0.49)×109/L、(2.29±0.28)×109/L;治疗组患者ALT水平在第8周为(259.70±9.49)U/L、第12周为(125.0±9.10)U/L、第24周为(92.0±10.60)U/L,分别显著低于同期对照组的(312.40±10.58)U/L、(335.0±8.50)U/L、(232.0±9.00)U/L;治疗组患者TBil在第12周为(14.0±4.00)μmol/L、第24周为(9.20±3.60)μmol/L,分别显著低于对照组的(28.2±9.60)μmol/L、(32.0±9.50)μmol/L;治疗组患者第72周HBV DNA阴转率为75%、HBeAg/HBeAb转换率为50%,显著高于对照组的51.3%、38.5%;治疗第48周后,HBsAg<1000 IU/ml的患者,治疗组有26例,对照组为15例。以上结果经统计学处理,差异有显著性意义(P<0.05)。结论:采用体现"补肾生髓成肝"治疗法则的"补肾健脾"方联合Peg-IFNα-2a治疗CHB,可以获得"减毒"(减少骨髓抑制,降低肝损伤)"增效"(提高病毒学应答)的生物学效应,增加患者的受益。

慢性乙型肝炎患者抗病毒治疗前后外周血CD4+CD25+调节性T细胞的变化

目的研究慢性乙型肝炎(乙肝)患者经聚乙二醇干扰素和阿德福韦抗病毒治疗前后外周血CD4+CD25+调节性T细胞(Treg)的变化情况。方法慢性乙肝患者35例,其中聚乙二醇干扰素α-2a(40KD)治疗(干扰素组)18例,阿德福韦酯治疗(阿德福韦组)17例;另收集肝炎病毒标志物阴性,肝功能正常的健康志愿者12例作对照。采集两治疗组治疗前及治疗12、24、48周时的外周血单个核细胞(PBMC),以流式细胞技术检测CD4+CD25+Treg细胞/PBMCs的百分比,并分析其与血清丙氨酸转氨酶(ALT)、乙肝病毒(HBV)DNA的相关性。结果 Treg/PBMCs的百分比,干扰素组和阿德福韦组在治疗前分别为(3.72±1.15)%和(3.63±1.02)%,与正常对照组(2.47±0.90)%相比,差异均有显著性(t分别为2.51、2.48,均P<0.05)。干扰素组经治疗后,CD4+CD25+Treg细胞的比例逐渐下降,治疗12、24、48周时的比率分别为(2.87±0.76)%、(2.75±0.72)%和(2.51±0.69)%,与治疗前相比,差异均有显著性(t分别为2.41、2.58、2.95,P分别<0.05、<0.05、<0.01)。阿德福韦组经治疗后,CD4+CD25+Treg细胞的比例与治疗前相比,差异无显著性(P>0.05)。CD4+CD25+Treg细胞与ALT的变化呈正相关(r=0.52,P<0.01),而与HBV DNA无明显的相关性(r=0.25,P>0.05)。结论慢性乙肝患者外周血CD4+CD25+Treg细胞升高,聚乙二醇干扰素抗病毒治疗能改善患者的免疫功能状态,降低CD4+CD25+Treg细胞比例;而阿德福韦抗病毒治疗对CD4+CD25+Treg细胞无影响。

聚乙二醇干扰素α-2a联合ETV治疗HBeAg阴性CHB临床研究

目的探讨聚乙二醇干扰素α-2a(Peg-IFNα2a)联合恩替卡韦(ETV)治疗HBe Ag阴性慢性乙型肝炎(CHB)48周的疗效及安全性。方法回顾性纳入2013年6月至2015年6月在首都医科大学附属北京佑安医院接受Peg-IFNα2a(135μg/周)联合ETV(0.5 mg/d)治疗的50例初治HBe Ag阴性CHB患者,收集基线和治疗过程中每12周的临床数据,包括HBV DNA和HBs Ag水平等,分析48周HBV DNA不可检测率、HBs Ag清除率及不良反应发生情况。结果 Peg-IFNα2a联合ETV治疗48周,全部患者HBV DNA低于检测值(<20 IU/m L);HBs Ag清除率及血清学转换率分别为24%和16%。不良反应主要表现为发热、乏力、脱发、食欲下降、皮疹和甲状腺功能减退,给予对症及支持治疗,均可继续原方案。结论 Peg-IFNα2a联合ETV可提高HBe Ag阴性CHB的HBs Ag清除率,且安全性良好,是值得探索的优化治疗策略之一。

治疗丙型肝炎的新药——聚乙二醇化干扰素α-2a

为改善干扰素α-2a(IFN α-2a)的药代动力学特性并提高其疗效,开发了一种皮下注射的聚乙二醇化新产品,即聚乙二醇化干扰素α-2a(PEGIFN α-2a)。PEG IFN α-2a每周1次给药与:IFN α-2a每周3次给药相比,治疗伴或不伴肝硬化的慢性丙型肝炎(CHC)病人,其持久的病毒学应答率(SVR)显著提高。与IFN α-2a单用或IFN α-2b与利巴韦林合用相比,PEGIFN α-2a可更好地改善CHC病人的生活质量。CHC病人对PEG IFN α-2a的耐受性与IFN α-2a相似,头疼、疲劳和肌痛是最常见的药物不良反应。

IFNL4和IL-28B基因多态性检测评估慢性乙型肝炎患者抗病毒治疗应答价值分析

目的探讨检测血干扰素λ4(IFNL4)和白介素-28B(IL-28B)基因多态性对慢性乙型肝炎(CHB)患者抗病毒治疗后应答的评估价值。方法2015年3月~2017年3月收治的CHB患者140例,均接受聚乙二醇干扰素α-2a治疗12个月。应用市售试剂盒检测外周血IFNL4和IL-28B基因多态性。结果在治疗结束时,在140例CHB患者中,108例(77.1%)获得应答,32例(22.9%)无应答;应答组IL-28Brsrs8099917位点基因TT型占比为88.9%,显著高于无应答组的68.8%(P<0.05);应答组血清ALT、AST和HBV DNA水平分别为(35.4±3.2)U/L、(38.6±2.1)U/L和(3.8±2.1)lg copies/ml,均显著低于无应答组的(61.5±4.8)U/L、(73.5±3.0)U/L和(5.2±3.1)lg copies/ml(P<0.05);125例IFNL4 TT/TT型患者血清ALT、AST和HBV DNA水平分别为(47.1±2.5)U/L、(49.1±1.6)U/L和(4.5±1.2)lg copies/ml,与15例TT/△G型患者的(48.0±2.1)U/L、(59.4±1.5)U/L和(4.7±1.3)lg copies/ml比,无显著性差异(P>0.05);118例IL-28B TT型患者血清ALT、AST和HBV DNA水平分别为(36.4±2.1)U/L、(38.9±2.7)U/L和(4.0±1.7)lg copies/ml,显著低于22例TG型患者【分别为(59.0±1.4)U/L、(72.1±1.1)U/L和(6.0±2.1)lg copies/ml(P<0.05)。结论CHB患者IFNL4rs368234815位点基因以TT/TT型和IL-28Brs8099917位点基因以TT型居多,检测IFNL4基因多态性可能对预测抗病毒疗效无明显指导意义,而检测IL-28B基因多态性可能对抗病毒疗效有一定的预测价值。

聚乙二醇干扰素α-2a联合利巴韦林治疗老年慢性丙型肝炎的疗效与安全性评价

目的观察聚乙二醇干扰素α-2a（PEG-IFNα-2a）联合利巴韦林（RBV）治疗中青年慢性丙型肝炎（CHC）患者和老年CHC患者的疗效与安全性。方法选择2008年1月至2012年6月收治的73例成年CHC患者,分为中青年组18-50岁和老年组（60岁以上）。所有患者均给予PEG-IFNα-2a注射液180μg、每周1次,同时口服RBV片300-400 mg/次、3次/日,均用药48周。观察患者的病毒学应答、肝功能、免疫功能及不良反应发生情况。结果两组患者治疗48周后,持续病毒性应答率（SVR）、丙氨酸氨基转移酶（ALT）、天门冬酸氨基转移酶（AST）、CD3＋,CD4＋,CD8＋,CD4＋/CD8＋、自然杀伤细胞（NK）等比较均无统计学差异（P〉0.05）。但老年组患者在白细胞下降、抑郁或焦虑、腹胀、心电图异常等4项不良反应的发生率显著高于中青年组（P〈0.05）。结论 PEG-IFNα-2a和RBV联用治疗老年CHC有效,但必须重视不良反应。

聚乙二醇干扰素联α-2a联合利巴韦林治疗慢性丙型肝炎合并血友病2例

聚乙二醇干扰素联合利巴韦林是最有效的抗丙型肝炎病毒(hepatitis C virus,HCV)治疗方案.对于合并血友病的慢性丙型肝炎的抗病毒治疗鲜见国内文献报道.本文报道2例丙型肝炎合并血友病患者,经给予HCV治疗疗效满意,现报道如下.

聚乙二醇干扰素α2a联合替诺福韦对耐药性乙肝患者肝功能及HBV-DNA转阴率的影响

目的探讨聚乙二醇干扰素α2a联合替诺福韦对耐药性乙肝患者肝功能及乙肝病毒脱氧核糖核酸(HBVDNA)转阴率的影响。方法方便选取该院2015年3月—2017年8月收治的76例耐药性乙肝患者以随机数字表法分组,观察组与对照组各38例,对照组采用替诺福韦治疗,观察组采用聚乙二醇干扰素α2a联合替诺福韦治疗,对两组疗效、肝功能、HBV-DNA转阴率、不良反应发生率进行观察。结果观察组与对照组治疗总有效率分别为89.47%、68.42%,两组差异有统计学意义(χ~2=5.067,P<0.05);观察组治疗后的各肝功能指标均优于对照组,差异有统计学意义(t=10.058、10.401、10.453,P<0.05),;观察组患者HBV-DNA转阴率为76.32%,明显较对照组52.63%高,差异有统计学意义(χ~2=4.653,P<0.05),两组不良反应发生率差异无统计学意义(χ~2=0.350,P>0.05)。结论聚乙二醇干扰素α2a联合替诺福韦治疗耐药性乙肝能改善患者肝功能,提高HBV-DNA转阴率,值得推广。

α-2b干扰素抑制动脉粥样硬化的实验研究

目的 :探讨α - 2b干扰素 (IFNα- 2b)抑制动脉粥样硬化 (AS)的体内机制。方法 :随机将家兔分为空白对照 (NC)组、动脉粥样硬化 (AS)组、病毒感染动脉粥样硬化 (V)组、干扰素治疗非病毒感染动脉粥样硬化 (IFN -Ⅰ )组、干扰素治疗病毒感染动脉粥样硬化 (IFN -Ⅱ )组。复制AS模型 ,于第 1、3、5、7周酶法测血清总胆固醇、甘油三脂。 7周后主动脉苏丹Ⅳ染色测AS斑块面积 /总面积 ,HE染色观察主动脉形态学改变。用免疫组化法测胸主动脉中的增殖细胞核抗原 (PCNA)和单纯疱疹病毒Ⅰ型 (HSV -Ⅰ )的表达 ,用原位杂交法测血小板衍生生长因子 β(PDGF - β)的表达程度。 结果 :NC组、IFN -Ⅰ组、IFN -Ⅱ组主动脉粥样硬化斑块面积小于AS组 (P <0 .0 5) ,AS组小于V组 (P <0 .0 5)。NC组、IFN -Ⅰ组、IFN -Ⅱ组PDGF -B的表达低于AS组、V组 (P <0 .0 5)。结论 :病毒可能是AS的始动因素 ,PDGF - β可能是促使血管平滑肌细胞 (VSMC)增生、AS进展的主要因素。IFNα- 2b通过抑制病毒和下调PDGF - βmRNA抑制VSMC的增生 ,可能是其抑制AS的形成及发展的重要机制之一。

α2b干扰素治疗慢性丙肝患者的临床研究

目的 探讨α2 b干扰素对慢性丙肝患者外周血单个核细胞 (PBMC)内 HCV的治疗效果。方法 采用国产α 2 b干扰素 (30 0 MU / d)治疗 ,3个月为一疗程 ,共 2个疗程 ,并设常规治疗组(Vit C、门冬氨酸 )为对照。于疗程结束后分别检测患者 PBMC内 HCV- RNA和血清内 HCV- RNA、抗 - HCV。结果 α 2 b干扰素治疗组 2个疗程后慢性丙肝患者 PBMC、血清内 HCV - RNA和抗 -HCV转阴率分别为 4 2 .31% (11/ 2 6 )、5 7.6 9% (15 / 2 6 )、6 5 .38% (17/ 2 6 ) ,常规治疗组慢性丙肝患者 PBMC、血清内 HCV- RNA和抗 - HCV转阴率分别为 13.6 4 % (3/ 2 2 )、2 2 .73% (5 / 2 2 )、2 7.2 7%(6 / 2 2 ) ,两组相比 ,差异有显著性 (P <0 .0 5 )。结论 α 2 b干扰素对 PBMC内 HCV- RNA具有肯定的治疗作用 ,其疗效优于常规治疗组。