聚乙二醇化干扰素α-2a 联合利巴韦林治疗慢性丙型肝炎合并甲状腺功能紊乱一例

聚乙二醇化干扰素（PegIFN）α-2a 联合利巴韦林治疗慢性丙型肝炎过程中,IFN α治疗可通过自身免疫和非自身免疫机制导致甲状腺功能异常。药物可以控制的甲状腺功能低下或亢进并非是干扰素应用的绝对禁忌症。本文介绍一例PegIFNα-2a 联合利巴韦林治疗慢性丙型肝炎中发生复杂甲状腺功能紊乱,在对症治疗、密切监测情况下成功完成干扰素疗程并获得持续病毒学应答的典型病例。     

聚乙二醇化干扰素α-2a、聚乙二醇化干扰素α-2b和干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的疗效

目的观察聚乙二醇化干扰素(PegIFN)α-2a、PegIFN-α-2b和干扰素(IFN)α-2b联合利巴韦林治疗慢性丙型肝炎(CHC)患者的疗效。方法回顾性观察278例CHC患者的临床资料,分为接受PegIFN-α-2a、PegIFN-α-2b和IFN-α-2b联合利巴韦林抗病毒治疗组。比较患者治疗前、治疗第4、12、24、48周时各组患者HCV基因分型、HCV RNA载量、ALT和AST的变化。分析各组患者治疗期间ALT/AST复常率、病毒学应答,不同基因型或HCV RNA载量与病毒学应答的相关性。结果停药后随访24周时,各治疗组患者肝功能复常率差异具有统计学意义(χ~2=23.06、P0.001),以PegIFN-α-2a(180μg)组与PegIFN-α-2b(80μg)组患者复常率较高(分别为76.7%和83.0%)。各治疗组患者快速病毒学应答(RVR)、治疗结束时病毒学应答(ETVR)及持续病毒学应答(SVR)差异均具有统计学意义(χ~2=9.79、P=0.04,χ~2=11.33、P=0.02,χ~2=11.99、P=0.02),以PegIFN-α-2a(180μg)组与PegIFN-α-2b(80μg)组患者较高(分别为62.8%、88.4%、64.0%和64.2%、83.0%、65.1%)。普通IFN-α-2b(600万单位)组、PegIFN-α-2a(180μg)组、PegIFN-α-2b(80μg)组患者依次有13例、54例和68例获得RVR,依次有11例(84.6%)、50例(92.6%)和62例(91.2%)最终获得SVR。入组患者中1b基因型患者243例,其RVR、完全早期病毒学应答(cE VR)和SVR均优于非HCV 1b基因型患者(χ~2=8.23、P0.001,χ~2=46.26、P=0.01,χ~2=10.22、P0.001)。普通IFN-α-2b(600万单位)组、PegIFN-α-2a(180μg)组、PegIFN-α-2b(80μg)组低病毒载量(HCV RNA6.0 Log_(10)拷贝/ml)患者的SVR均优于高病毒载量患者(χ~2=4.10、P=0.04,χ~2=20.89、P0.001,χ~2=19.60、P0.001)。结论聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎具有较好疗效,早期RVR对SVR的获得具有很强的预测作用,非基因HCV 1b型和低病毒载量患者疗效优于HCV 1b基因型和高病毒载量患者。     

慢性丙型肝炎患者应用聚乙二醇干扰素α-2a和2b病毒学应答比较

目的 比较慢性丙型肝炎患者接受聚乙二醇干扰素α( Peg IFNα) -2a或Peg IFNα-2b联合利巴韦林治疗后的疗效差异.方法 对46例慢性丙型肝炎(CHC)患者进行回顾性分析,将患者分为2组,Peg IFNα-2a组24例,每周1次皮下注射Peg IFNα-2a 180μg,Peg IFNα-2b组22例,1...     

小剂量PEG-INF-α-2a联合利巴韦林治疗肾移植后丙型肝炎的疗效及安全性

目的 探讨小剂量聚乙二醇干扰素α-2a(PEG-INF-α-2a)联合利巴韦林治疗肾移植后丙型肝炎的疗效及安全性.方法 移植前血清抗丙型肝炎病毒(HCV)抗体阳性和(或)HCV RNA持续阳性者13例,随机分为试验组(7例)和对照组(6例),试验组术后给予PEGINFα2a和利巴韦林治疗16周,其中4例延长至48周;对照组给予普通护肝和抗炎治疗;两组均随访2年以上.结果 试验组治疗16周后有5例获得早期应答,其中4例获得完全应答,没有无效病例,明显优于对照组;丙氨酸转氨酶和天冬氨酸转氨酸基本正常,明显好于对照组.4例治疗48周者,1例35周时因严重面部肌肉痛并血肌酐升高,病理证实为体液性排斥反应,停止治疗;1例38周时因HCV RNA复制增加,停止治疗.试验组治疗后2年时5例达到完全应答,其中2例抗HCV抗体转阴,HCV RNA明显低于对照组,肝功能基本维持正常,血肌酐高于对照组(P＞0.05).该方案治疗的不良反应有发热、肌肉痛、粒细胞缺乏症和(或)贫血和体液性排斥反应,经停药和对症处理痊愈.结论 小剂量PEG-INF-α 2a联合利巴韦林对肾移植合并丙型肝炎者有明确疗效,16周的疗程效果较为理想,但应注意PEG-INF-α-2a可诱发体液性排斥反应和致血肌酐爬行升高.     

聚乙二醇化干扰素联合利巴韦林治疗肝移植术后丙型肝炎复发

目的 探讨聚乙二醇化干扰素(PEG-IFNα)联合利巴韦林治疗肝移植术后丙型肝炎复发的效果及安全性.方法 回顾性分析9例丙型肝炎相关终末期肝病患者接受肝移植的临床资料,其中5例受者术后出现丙型肝炎复发,均给予PEG-IFNα-2a联合利巴韦林抗HCV治疗,疗程为48周.观察治疗前后血红蛋白、白细胞计数、移植肝功能及HCV RNA复制水平等指标的变化,评估治疗后的早期病毒应答(EVR)、持续性病毒应答(SVR)及不良反应等.结果 5例受者中有3例在治疗12周内达到EVR,并在治疗后获得SVR,移植肝功能也恢复正常;1例因在治疗12周后HCVRNA的下降达不到2个对数级而停药,1例虽HCV RNA下降2个对数级以上,但治疗至24周时HCV RNA未转阴而停药,至48周时HCV RNA均维持在较低水平.5例丙型肝炎复发受者在治疗后均发生白细胞减少和(或)发热等不良反应,给予对症处理后好转.结论 PEG-IFNα联合利巴韦林治疗肝移植后丙型肝炎复发安全性好,多数受者可取得持续性病毒学应答.     

聚乙二醇化干扰素联合利巴韦林治疗肝移植后丙型肝炎复发四例

目的 探讨聚乙二醇化干扰素(PEG-IFNα-2a)联合利巴韦林(RIB)方案治疗肝移植后丙型肝炎复发的临床疗效.方法 回顾性分析4例肝移植术后丙型肝炎复发患者的临床资料.4例患者中,术前诊断丙型肝炎合并肝硬化3例,丙型肝炎后肝硬化合并肝细胞肝癌1例,术后均采用他克莫司+霉酚酸酯+皮质激素的三联免疫抑制方案.术后8～12周时,患者均经移植肝组织活检证实丙型肝炎复发.复发后,立即采用PFG-IFNα-2a联合RIB方案进行抗丙型肝炎治疗,连续治疗48周.PEG-IFNα-2a的用量为180μg,皮下注射,每周1次;RIB的用量为1000 mg/d,口服.在治疗期间,检查患者的血常规、肝肾功能、丙型肝炎病毒核糖核酸及移植肝组织活检,观察生化学应答、持续病毒学应答及组织学应答等指标.结果 除1例外,其他患者经治疗后出现持续病毒学应答,移植肝功能均恢复正常,在术后0、48和72周,移植肝组织病理学炎症坏死和纤维化情况改善.1例在术后第7天经组织学证实发生急性排斥反应,给予连续3 d皮质激素冲击治疗后,病情好转.无患者因严重的不良反应而停药或退出治疗.结论 PEG-IFNα-2a联合RIB方案是治疗肝移植后丙型肝炎复发的有效方法,患者的耐受性好,不良反应少.     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎的疗效及影响因素分析

目的：分析聚乙二醇化干扰素（PegIFN）联合利巴韦林治疗对慢性丙型肝炎的疗效及影响因素。方法使用聚PegIFNα-2a（派罗欣180μg/周）联合利巴韦林（根据体重900～1200 mg/d）治疗60例慢性丙型肝炎患者,疗程48周。结果本研究60例慢性丙型肝炎患者中,HCV-Ⅰ型45例,占75%,非HCV-Ⅰ型15例,占25%。HCV-Ⅰ型和非HCV-Ⅰ型患者持续应答（SVR）率分别为60.0%和93.3%,差异具有统计学意义（χ2=6.162,P=0.013）;基线病毒载量,以HCV RNA定量1＆#215;106 IU/ml划分,HCV RNA高水平组和低水平组SVR分别为48.3%和77.3%,差异具有统计学意义（χ2=6.093,P=0.014）。治疗过程中获得快速病毒学应答（RVR）的病例获得SVR和未获得RVR的病例获得SVR的比率分别为84.6%和38.1%,差异具有统计学意义（χ2=9.690,P=0.002）。治疗过程中获得早期病毒学应答（EVR）的病例获得SVR和未获得EVR的病例获得SVR的比率分别为78.4%和11.1%,差异具有统计学意义（χ2=4.036,P=0.045）。结论慢性丙型肝炎患者的治疗过程中,病毒基因型、基线病毒载量以及治疗过程中是否获得RVR/EVR均可能影响治疗后的持续病毒学应答。     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响因素

目的探讨聚乙二醇化干扰素（PegIFN）联合利巴韦林（RBV）治疗慢性丙型肝炎疗效的影响因素。 方法回顾性分析2008年1月至2011年12月于宝鸡市中心医院接受PegIFN和RBV联合治疗的148例HCV感染者的临床资料。采用持续性病毒应答24周（SVR24）、早期病毒学应答（EVR）、治疗结束病毒应答（ETR）、持续性病毒应答12周（SVR12）、复发、无效应答、病毒学突破评估疗效,Logistic回归分析影响疗效的因素。 结果148例HCV感染者失访12例（8.1%）。136例HCV感染者中128例（94.1%）患者出现EVR、118例（86.8%）患者出现ETR、114例（83.8%）患者出现SVR12、112例（82.4%）患者出现SVR24、8例（5.9%）患者无效应答、6例（4.4%）患者复发、4例患者出现病毒学突破（2.9%）。HCV RNA、HCV基因型和UA均为影响HCV感染者SVR24的因素（P均< 0.05）。 结论PegIFN联合RBV治疗HCV感染疗效显著。HCV基因型2/3、HCV RNA水平较低和尿酸与HCV SVR相关。     

聚乙二醇干扰素α-2b治疗HBeAg阴性和阳性慢性乙型肝炎疗效分析

HBeAg阴性与HBeAg阳性CHB在流行病学、发病机制、自然病程、预后和治疗等方面都截然不同[1-2].本研究旨在探讨聚乙二醇干扰素α-2b(Peg IFNα-2b)在HBeAg阴性和HBeAg阳性CHB抗病毒治疗中的差异,同时评估影响应答的相关因素. 1 资料与方法 1.1 研究对象选取2007年1月至2009年6月在杭州市第六人民医院用PegIFNα-2b治疗的88例CHB患者,其中HBeAg阴性31例,HBeAg阳性57例.PegIFNα-2b的用法:1～ 1.5 μg/kg,1次/周,皮下注射,连续48周,治疗期间不使用其他抗病毒药物及保肝药物.所选病例均符合《慢性乙型肝炎防治指南(2010年版)》[3]中IFN治疗的适应证.所有患者均签署知情同意书,治疗方案经医院伦理委员会批准.     

解读2011年美国肝脏病学会关于基因1型慢性丙型肝炎治疗指南的更新

慢性丙型肝炎病毒（HCV）感染的标准抗病毒治疗方案是聚乙二醇化干扰素-α（Peg-IFN-α）2a或Peg-IFN-α2b联合利巴韦林（RBV）治疗。基因1型慢性丙型肝炎初治患者48周的SVR为40%～54%,复发率大约为15%～25%[1]。随着直接作用（direct-acting antiviral,DAA）抗病毒药物的研发,     

Pegylated interferon alfa-2a and ribavirin for recurrent hepatitis C after liver transplantation

BACKGROUND: Recurrent hepatitis C virus (HCV) is often treated with interferon and ribavirin combination therapy but results have been disappointing. Given the promising results reported with pegylated interferon and ribavirin for hepatitis C, this combination is now preferred for the treatment of recurrent HCV. This article reports a transplantation program's experience with antiviral therapy treatment for liver transplant recipients with recurrent HCV. METHODS: Between October 2002 and June 2004, patients with recurrent HCV were screened to determine if they were eligible for treatment. Liver function tests, HCVRNA, and liver biopsies were done on all patients prior to treatment. HCVRNA was repeated at 3 months, end of treatment (EOT), and 6 months after EOT for patients HCVRNA-negative at EOT. Patients were prospectively followed up after starting weekly pegylated interferon alfa-2a 180 mcg/wk and ribavirin 1000-1200 mg/d (Roche, Nutley, NJ, United States) with folic acid 1 mg/d. RESULTS: Thirty-two patients were eligible for treatment with a median age of 49.2 years. Twenty-one patients have completed treatment, 6 remain on treatment, and 5 were intolerant. In an intention-to-treat analysis, sustained HCVRNA eradication occurred in at least 40.6% of patients. Side effects led to treatment withdrawal in 5 patients (15.6%). CONCLUSION: Pegylated interferon alfa-2a and ribavirin appear promising for the treatment of recurrent HCV. Side effects were an infrequent cause of treatment discontinuation, unlike previous combinations of interferon-based therapy. Randomized, prospective trials incorporating serial liver biopsies with appropriate quality of life analyses are required to manage this silent epidemic.     

Intravesical interferon alfa-2b administration in the treatment of superficial bladder tumors

This study was undertaken to assess the value of intravesical interferon alfa-2b treatment in preventing the recurrences of superficial transitional cell carcinoma of the bladder. A total of 30 patients aged from 33 to 78 entered the protocol. The intravesical instillations were performed once a week for 8 weeks. A solution of 10 x 10(6) IU interferon alfa-2b in 30 ml of normal saline was used. Follow-up ranged from 12 to 28 months. Of the 30 patients, 19 (63.33%) were tumor free at the end of follow-up. Of the remaining 11 patients, 7 presented with recurrent superficial tumors and 4 with invasive bladder tumors. No side effects were noted.     

Suppression of in vitro proliferative scar fibroblast contraction by interferon alfa-2b

Increased fibroblast activity and collagen production have been observed frequently in proliferative scars. Previous studies have demonstrated that interferons suppress collagen production by means of normal, keloid, and hypertrophic scar-derived fibroblasts. The fibroblast-populated collagen lattice is an in vitro model used to study fibroblast function. We used fibroblast-populated collagen lattices to evaluate the effect of interferon on fibroblasts harvested from normal human skin, human keloid, and hypertrophic scar tissues. Human recombinant interferon alfa-2b (1000 IU/ml) was added to the culture media. The collagen gel, prepared from rat tail tendon bundles, was overlaid with 5 x 10(4) fibroblast cells. Keloid fibroblast-populated collagen lattices showed the highest contraction. Contraction in all the groups appeared suppressed by interferon alfa-2b during the first 72 hours of study (p < 0.05). The reduction in fibroblast-populated collagen lattice contraction by interferon alfa-2b was similar among the groups. The contractile properties of fibroblasts taken from normal human skin, keloids, and hypertrophic scars in this in vitro study were suppressed by interferon alfa-2b. This suggested that interferon alfa-2b may be beneficial for the treatment of proliferative scars.     

Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with chronic hepatitis C.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with liver dysfunction and hepatocellular carcinoma. In patients with normal kidney function, treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV) frequently leads to eradication of HCV. Treatment in dialysis patients has long been controversial and until recently, the use of RBV was considered to be contra-indicated. We used plasma trough levels of RBV to promote tolerance, safety and efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly via hepatic metabolism. METHODS: Seven haemodialysis patients with chronic HCV infection were eligible and started with 135 microg PEG-IFN alfa-2a (40 kD) weekly and 200 mg RBV every other day. Dose adaptations were allowed following study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12, 24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels were monitored regularly by HPLC-technique. RESULTS: All patients completed the treatment. In two patients, the PEG-IFN dose had to be reduced to 90 microg/week because of adverse events. To achieve the target range (1.5-2.5 microg/ml) of the plasma trough level, the mean RBV dose was increased to a dose between 133 and 200 mg each day in five patients. Despite an increase of the weekly erythropoietin (Epo) dose, two to a max of four red cell transfusions were given to four patients. A sustained viral response (SVR) was reached in five patients (3/5 with genotype 1/4 and 2/2 with genotype 2/3). CONCLUSION: In our series of seven patients, we were able to use RBV monitoring drug levels in combination with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However, Epo and transfusion requirements may increase. In two patients adverse events were observed, but manageable with dose reduction of PEG-IFN.     

Chronic ductopenic rejection in patients with recurrent hepatitis C virus treated with pegylated interferon alfa-2a and ribavirin

BACKGROUND: Interferon use for post liver transplantation (LT) recurrent hepatitis C (HCV) has not consistently been associated with acute cellular rejection (ACR). We examined the incidence of chronic ductopenic rejection (CR) in patients receiving pegylated interferon alfa-2a and ribavirin (PEG) to treat recurrent HCV. METHODS: A chart review of 12 patients developing CR while receiving an escalating dose regimen of PEG with protocol liver biopsies every 6 months was conducted. Values are shown as median (range). RESULTS: Twelve of the 70 patients treated with PEG developed CR. Median age at LT was 53 (37-63) years; immunosuppression consisted of tacrolimus or cyclosporine with prednisone. PEG was started at 3.6 (0.2-13.5) years after LT. Two patients had one episode of ACR before PEG. Four patients had first ACR while receiving PEG. CR was diagnosed after 12 (4-17) months of PEG; by then 8 patients had undetectable HCV-RNA. Tacrolimus and cyclosporine levels (ng/mL) were 7.9 (3.2-18.9) and 76 (71-93) before PEG, and 6.9 (3.7-9.7) and 130 (81-153) at CR. Six patients were treated more than 1 year with PEG; three had undetectable HCV-RNA when CR was diagnosed. Five patients are being treated for CR; one has been listed for LT; two patients were retransplanted. Five patients died as a result of sepsis partially related to CR. CONCLUSIONS: Treatment with pegylated-interferon alpha-2a and ribavirin may trigger rapidly progressive CR in patients with therapeutic immunosuppressive trough levels, with or without first inducing ACR.     

Combination therapy with capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma: a phase II study

Capecitabine is a fluoropyrimidine carbamate capable of exploiting the high concentrations of thymidine phosphorylase in tumor tissue to achieve activation preferentially at the tumor site. Thymidine phosphorylase activity is high in renal cell carcinoma tissue. Interferon alfa has been proved to be the agent for standard therapy in metastatic renal cell carcinoma. The purpose of the study was to assess the efficacy and toxicity of combining capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma. Twenty-five patients with advanced renal cell carcinoma and no prior systemic therapy were treated with the combination of capecitabine at a dose of 1,250 mg/m2 twice daily for 2 weeks after every 21 days and interferon alfa-2A 6 million U three times a week. The overall response rate was 24.0% (95% CI, 9.4-45.1%), from 6 responded patients 5 had partial responses and 1 complete response. Stable disease status was achieved in 9 patients (36.0% with 95% CI 18.0-57.5%). The median survival time was 248 days (95% CI, 173-265 days). The median time to progression was 126 days (95% CI, 49-165 days). Grade 3-4 toxicities occurred in 12 patients and included fatigue (33.3%), nausea, hand-foot syndrome (both 12.5%), anorexia (8.3%), vomiting, anemia and neutropenia (all 4.2%). The capecitabine and interferon alfa-2A combination has clinical activity and an acceptable toxicity profile in patients with metastatic renal cell carcinoma. The importance of adding capecitabine to interferon alfa needs to be confirmed in a randomized trial.     

Interim results from a national multicenter phase II trial of combination bacillus Calmette-Guerin plus interferon alfa-2b for superficial bladder cancer

PURPOSE: Interim results are provided from a large multicenter trial of combination bacillus Calmette-Guerin (BCG) plus interferon (IFN) alfa-2b for BCG naive (BCG-N) and previous BCG failure (BCG-F) cases of superficial bladder cancer. MATERIALS AND METHODS: A total of 490 patients enrolled from May 1999 to May 2000 with a median of 24 months of followup were analyzed. The BCG-N group (259) was treated with a 6-week induction course of standard dose BCG plus 50 million units of IFN followed by 3, 3-week maintenance cycles of reduced dose BCG (1/3 to 1/10) plus 50 million units IFN at 3, 9 and 15 months after induction. The BCG-F group (231) was treated similarly except induction therapy began at a decreased (1/3 to 1/10) BCG dose. RESULTS: The simple tumor recurrence rates for BCG-N and BCG-F groups were 40% and 52%, and the Kaplan-Meier estimates for disease freedom at 24 months were 57% and 42%, respectively. Progression to muscle invasion occurred in 5% and 4.3% while metastasis occurred in 2.3% and 2.6%, respectively. In each group 3.9% of patients underwent cystectomy and 2 patients in each group died of bladder cancer. Serious adverse events occurred in 5.5% with infection related serious adverse events being less prevalent in the BCG-F group (2.6% vs 5.4%). Toxicity related dropout, treatment delay and/or further BCG dose reduction, and need for symptomatic drugs were similar. Moderate to severe local side effects during induction were higher in the BCG-F group (6.2% vs 16.9%) but equilibrated during maintenance therapy. Systemic reactions were rare. CONCLUSIONS: This multicenter trial provides a benchmark for the efficacy and safety of combination BCG and IFN as up front and salvage therapy. The incremental value of IFN cannot be determined from this study.     

Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation

Recurrent hepatitis C is often treated with an interferon and ribavirin combination therapy, but the results have been disappointing. Given the promising results reported with pegylated interferon and ribavirin for hepatitis C, we were interested in evaluating the effectiveness of this treatment in liver transplant recipients with recurrent hepatitis C (HCV). METHODS: Between November 2001 and September 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Liver function tests, HCV-RNA, and liver biopsies were performed on all patients prior to treatment. HCV-RNA was repeated at 3 months, the end of treatment (EOT), and 6 months after EOT for patients who were HCV-RNA negative at EOT. Patients were prospectively followed after starting weekly pegylated interferon alfa-2b 1.5 mcg/kg per week and ribavirin 800 mg per day (Schering-Plough, Kenilworth, NJ, USA) with folic acid 1 mg per day. RESULTS: Thirty-nine patients eligible for treatment displayed a median age of 50.4 years. Eighteen patients completed treatment, 4 remain on treatment, and 17 were intolerant. Sustained HCV-RNA eradication occurred in 66.7% of patients who completed treatment. Side effects led to treatment withdrawal in 17 patients (43.6%) In an intention-to treat analysis, sustained HCV-RNA eradication occurred in 30.8% of patients. CONCLUSION: Side effects are an important limiting factor in the treatment of recurrent HCV with pegylated interferon and ribavirin. However, these results are encouraging as sustained HCV eradication occurred in at least 66.7% of patients who completed treatment. Prospective randomized trials are required to assess the effectiveness of this treatment and its impact on quality of life and histology.