干扰素治疗慢性病毒性肝炎发生甲状腺功能异常的临床特征和危险因素

目的 探讨IFN治疗慢性病毒性肝炎患者发生甲状腺功能异常的临床特征,并结合生物化学、病毒学等因素分析其危险因素.方法 选择2007年1月至2010年3月间采用IFN治疗的慢性乙型和丙型肝炎患者385例,在抗病毒治疗前2周内及治疗中每4～12周检测血常规、肝功能和病毒载量,并观察甲状腺功能的血清学指标和甲状腺自身抗体变化,治疗结束后继续随访48周.Logistic分析甲状腺功能异常发生的危险因素.结果 IFN治疗后发生甲状腺功能异常者共32例,发生率为8.3％,其中甲状腺功能亢进及减退各占一半,依次为桥本甲状腺炎10例,Graves病和破坏性甲状腺炎各8例,非自身免疫性甲状腺功能减退6例.10例甲状腺功能异常者有明显临床症状;9例进行内分泌治疗,3例停用IFN.发生甲状腺功能异常的中位时间为治疗第7个月(最早于治疗第2个月,最迟于治疗结束后7个月),甲状腺功能异常持续时间中位数为4个月(1～11个月).治疗结束后随访1年,所有患者甲状腺功能均恢复正常.女性(OR=3.656)和预存的抗甲状腺过氧化物酶抗体(OR=1.006)是发生甲状腺功能异常的独立危险因素.结论 Graves病、桥本甲状腺炎、破坏性甲状腺炎和非自身免疫性甲状腺功能减退是IFN致甲状腺功能异常的主要类型,前两者通常伴有明显症状,可能需停用IFN并予内分泌治疗.接受IFN治疗的慢性病毒性肝炎患者在治疗前、中及后均应密切监测甲状腺功能和甲状腺自身抗体,尤其是女性及有预存甲状腺自身抗体者.     

聚乙二醇干扰素α-2a治疗慢性丙型肝炎甲状腺功能异常分析

目的：探讨应用聚乙二醇干扰素α-2a治疗慢性丙型肝炎时甲状腺功能异常情况及对策。方法对2010年10月至2013年10月应用聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者186例,治疗前及治疗后12周、24周、36周、48周分别检测甲状腺功能,引起甲状腺功能严重异常者给予相应的治疗。结果在应用聚乙二醇干扰素α-2a治疗期间甲状腺功能始终正常137例,占73．66％;出现甲状腺功能异常的患者49例,占26．34％,其中男19例,女30例,女性甲状腺功能异常者显著高于男性（χ2＝29．27,P＜0．005）;甲亢1例,亚甲亢7例,甲减4例,亚甲减12例,24例甲亢、亚甲亢、甲减及亚甲减中,甲亢、亚甲亢占33．33％,甲减、亚甲减占66．67％;其他形式的甲状腺功能异常25例。抗甲状腺球蛋白抗体和甲状腺过氧化物酶抗体增高18例,占9．68％;甲状腺功能严重异常者给予相应的治疗,除1例甲亢患者停用聚乙二醇干扰素外,其余患者均完成了规定疗程。结论聚乙二醇干扰素α-2a治疗慢性丙型肝炎可导致甲状腺功能异常,应密切观察甲状腺功能,女性患者干扰素治疗时易引起甲状腺功能异常,甲减、亚甲减多于甲亢、亚甲亢,聚乙二醇干扰素a-2a可能诱发甲状腺自身免疫,甲状腺功能严重异常的经积极治疗,可以保证聚乙二醇干扰素的继续进行,完成疗程。     

干扰素治疗慢性丙型肝炎导致甲状腺疾病的临床分析

目的分析干扰素治疗慢性丙型肝炎患者导致甲状腺疾病的发病情况。方法对105例慢性丙型肝炎患者,分为治疗组和对照组,回顾总结各组甲状腺疾病的发病率,并进行统计学分析。结果治疗组甲状腺疾病的发病率为21.33%,对照组甲状腺疾病的发病率为10.00%,两组的发病率差异有统计学意义(p0.05)。治疗组中,桥本氏甲状腺炎发病率最高(8.00%),其次为甲亢(5.33%),甲减(4.00%),无痛性甲状腺炎(2.67%)。结论慢性丙型肝炎病毒感染与甲状腺疾病相关,且干扰素治疗慢性丙型肝炎可明显增加甲状腺疾病的发病率。     

干扰素联合病毒唑治疗慢性丙型肝炎诱发甲状腺功能亢进2例

例 1　男性 ,34岁。 1997年 4月查体发现肝功异常 ,经用一般保肝药物治疗 6个月无效 ,于 1997年 10月就诊本院。患者于 7年前曾因病输血浆2 0 0毫升 ,家族中无遗传性及自体免疫性疾病。查体 :无明显阳性体征。实验室检查 :ＡＬＴ 2 78Ｕ /Ｌ、ＡＳＴ 2 12Ｕ/Ｌ、ＳＢ 12 μｍｕｌ/Ｌ、白蛋白 4 2 ｇ/Ｌ、球蛋白30 ｇ/Ｌ。甲、乙、戊型肝炎病毒血清标记物均阴性 ,抗ＨＣＶ阳性 ,ＰＣＲ法测ＨＢＶＤＮＡ阴性、ＨＣＶＲＮＡ阳性。Ｂ超提示慢性肝病。临床诊断 :慢性丙型肝炎。 1997年 11月 3日开始干扰素联合病毒唑抗病毒治疗。干扰素α - 2ｂ(…     

冷球蛋白血症对慢性丙型肝炎抗病毒治疗后甲状腺功能的影响

目的 探讨冷球蛋白血症（MC）对慢性丙型肝炎（CHC）抗病毒治疗后甲状腺功能的影响.方法 将102例慢性丙型肝炎患者分为冷球蛋白血症阳性组（44例）和阴性组（58例）,两组患者均予聚乙二醇干扰素（PEG-IFN） α-2a联合利巴韦林治疗,并检测治疗前、治疗后12周、24周、36周、48周及治疗结束后24周患者血清HCV RNA和甲状腺功能,观察治疗前后甲状腺功能的变化.结果 102例慢性丙型肝炎患者中冷球蛋白阳性44例,阳性率为43.1％（44/102）.冷球蛋白血症阳性组持续病毒学应答发生率（SVR）低于阴性组（59.1％比81.0％,P＜0.05）;冷球蛋白血症阳性组治疗12周、24周甲状腺功能异常新发病例均高于阴性组（P＜0.05）.以亚急性甲状腺机能减退为主要表现形式;冷球蛋白血症阳性组12周、24周时甲状腺功能异常发病率均高于阴性组（P＜0.05）.甲状腺功能异常者多数在治疗36周时恢复正常,均能完成48周疗程.结论 慢性丙型肝炎合并冷球蛋白血症阳性的患者干扰素治疗后更易出现甲状腺功能异常,但甲状腺功能改变不影响继续治疗.     

干扰素联合利巴韦林治疗慢性丙型肝炎致甲状腺功能异常临床分析

目的探讨IFN联合利巴韦林(RBV)治疗CHC致甲状腺功能异常的临床特点。方法回顾性分析78例CHC患者应用干扰素联合RBV治疗过程中出现甲状腺功能异常的临床资料。78例患者随机分为重组人干扰素α2b(IFN-α2b)组58例,聚乙二醇化干扰素α-2a(Peg-IFN-α2a)组20例。结果 78例患者中,发生甲状腺功能异常(TD)者17例(21.79%),其中甲状腺功能亢进症5例,甲状腺功能减退症12例。78例患者的性别、基线HCV RNA载量、丙型肝炎病程、病毒应答时间、总疗程与TD发生无显著相关性,年龄、既往TD病史有显著相关性。78例患者中,有15例为一过性TD,仅2例终止干扰素治疗。两组患者导致TD的发生率分别为10%(2/20)和25.80%(15/58)。两组患者的年龄(χ2=4.974,P=0.026,OR=1.073)、既往TD病史(χ2=5.123,P=0.024,OR=16.569)与甲状腺疾病发生呈现正相关。出现TD时间主要集中在干扰素治疗后31~60天。结论 TD是干扰素治疗CHC中较常见的不良反应,特别是既往有TD病史者,多数TD为短暂性异常,应在密切监视下完成抗病毒疗程。     

慢性丙型肝炎与甲状腺疾病的关系及α-干扰素治疗的影响

有学者认为慢性丙型肝炎病人易并发甲状腺疾病,α-干扰素治疗可诱导产生自身抗体,从而加重甲状腺疾病,故临床医师对α-干扰素治疗慢性丙型肝炎心存疑虑。近来多项实验对此进行了研究。 Nduwayo L等检测了 215例慢性丙型肝炎病人血清中的抗甲状腺过氧化物酶抗体和抗甲状腺球蛋白抗体,发现其发生率和普通人群相似。Marazuela     

慢性丙型肝炎合并甲状腺功能异常研究进展

慢性丙型肝炎合并甲状腺功能异常主要表现为促甲状腺激素、甲状腺素和三碘甲状腺原氨酸水平的改变及抗甲状腺球蛋白抗体和抗过氧化物酶抗体阳性率增高等方面的变化。检测这些相关物质,对评估肝功能、判断病程、预防甲状腺病的发生有重要的临床意义。     

Interferon-alpha induced and ribavirin induced thyroid dysfunction in patients with chronic hepatitis C

Chronic hepatitis C (CHC) is one of the commonest infectious diseases of the liver and may lead to cirrhosis or hepatocellular carcinoma. Combination therapy with pegylated interferon (PEG-IFN) and Ribavirin is the treatment of choice for CHC. Combination therapy is thought to act by means of antiviral mechanisms and immunomodulation. Thyroid dysfunction is the most common autoimmune adverse effect associated with combination therapy; hypothyroidism is more common than hyperthyroidism. Antithyroid antibodies and female sex have a predictive value in the development of interferon induced thyroid disease (IITD). Patients with CHC should be informed of the possibility of side effects on the thyroid gland. Screening for antithyroid antibodies and thyroid function tests should be performed in patients with CHC before the commencement of antiviral treatment, and during and after it. This article reviews different aspects of IITD, including its pathogenesis, clinical manifestations, association with treatment regimens and treatment response and the outcome of thyroid dysfunction.     

Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C

AIM： To study predictive factors of thyroid dysfunction associated with interferon-alpha （IFNa） therapy in chronic hepatitis C （CHC） and to describe its long-term evolution in a large population without previous thyroid dysfunction. METHODS： We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004. RESULTS： Thyroid disorder developed in 30/301 （10%） patients with a mean delay of 6 ± 3.75 mo： 13 patients had hyperthyroidism, 11 had hypothyroidism, and 6 had biphasic evolution. During a mean follow-up of 41.59 ± 15.39 mo, 9 patients with hyperthyroidism, 3 with hypothyroidism, and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo. Recovery rate of dysthyroidism was not modified by treatment discontinuation, but was better for patients with negative thyroid antibodies before antiviral treatment （P = 0.02）. Women had significantly more dysthyroidism （P = 0.05）. Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism （P 〈 0.0003 and P = 0.0003, respectively）. In a multivariate model, low fibrosis was found to be a predictive factor of dysthyroidism （P = 0.039）.
CONCLUSION： In this monocentric population of CHC, dysthyroidism, especially hyperthyroidism, developed in 10% of patients, Low fibrosis was found to be a predictive factor of dysthyroidism, Thyroid disorder recovered in 16/30 patients （53%） and recovery was better in the non-autoimrnune form,     

慢性丙型肝炎干扰素治疗后复发患者的干扰素再治疗

目的探讨干扰素(IFN)治疗后复发的慢性丙型肝炎患者对IFN再治疗的应答情况及影响因素。方法对聚乙二醇化干扰素(PEG-IFN)α-2a与重组人干扰素(CIFN)α-2a治疗中国慢性丙型肝炎患者疗效与安全性的随机、开放、多中心对照研究中的6O例干扰素治疗后复发患者的再治疗进行回顾性研究。其中PEG-IFN α-2a组35例和CIFN α-2a组25例,以持续病毒学应答(SVR)作为疗效的主要评价指标,分析HCV RNA载量、基因型、药物种类对IFN疗效的影响。结果 60例复发患者用IFN再治疗后,55．00％取得治疗结束时的病毒学应答(ETVR),35．00％取得SVR;其中PEG-IFN α-2a组74.29％取得ETVR,显著高于CIFN α-2a组(28．00％),P<0．01; PEG-IFN α-2a组45．71％取得SVR,高于CIFN α-2a组(20．00％), P>0．05;病毒载量高、低组间的ETVR、SVR的差异无统计学意义;对于HCV基因1型感染患者,PEG- IFN α-2a的ETVR(75．00％)和SVR(45．83％)均显著高于CIFN α-2a组(分别为22．22％和11．11％), P相似文献   

慢性丙型肝炎干扰素治疗后复发患者干扰素联合利巴韦林再治疗

目的 探讨干扰素（IFN）治疗后复发的慢性丙型肝炎（CHC）患者对IFN联合利巴韦林再治疗的应答情况及影响因素。方法 100例IFN治疗后复发的CHC患者中，50例使用聚乙二醇干扰素α-2a（PEG—IFNα-2a），50例使用重组人干扰素α-1b（CIFNα—1b），均联合利巴韦林再治疗，联合治疗48周，停药随访24周，分析HCVRNA载量、病毒基因型、药物种类对联合治疗疗效的影响。结果 100例复发患者联合再治疗后，36．00％取得持续病毒学应答（SVR），其中PEG-IFNα-2a组48．00％取得SVR，显著高于CIFNα—1b组（24．00％，P〈0．05）。56例低病毒载量（HCV-RNA〈1×10^5拷贝／mL）患者中，PEG—IFNα-2a组28例，其中57．14％取得SVR，显著高于CIFNα—1b组（25．00％，P〈0．05）。HCV非基因1（2a或2b）型组29例，其中55．17％取得SVR，显著高于基因1型组（28．20％，P〈0．05）；在CIFNα—1b治疗组，病毒非基因1型17例患者，其中47．06％取得SVR，明显高于基因1型患者（12，12％，P〈0．01）；在基因1型组，PEG—IFNα-2a组38例，其中42．11％取得SVR，显著高于CIFNα—1b组（12．12％，P〈0.01）。结论 IFN治疗后复发的CHC患者IFN联合利巴韦林再治疗存在部分患者无应答；对于HCV病毒载量低、基因1型的复发患者，聚乙二醇干扰素联合利巴韦林再治疗疗效明显优于普通干扰素的联合治疗。     

慢性丙型肝炎患者心血管疾病研究进展

丙型肝炎病毒（HCV）具有嗜肝性和泛嗜性,除造成肝脏损伤外,也表现出大量的肝外表现。近年来研究表明,慢性丙型肝炎患者心血管疾病发生率较高。HCV感染可造成动脉粥样硬化、心肌病、心肌炎、肺动脉高压等,成为心血管疾病的危险因素。     

Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin tends to develop in patients with hypertension.     

Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.     

重组复合干扰素治疗慢性丙型肝炎的临床研究

目的 比较两种剂量的重组复合干扰素（Ｃｏｎｓｅｎｓｕｓ Ｉｎｔｅｒｆｅｒｏｎ,ＣＩＦＮ）和重组干扰素α－２α（ＩＦＮα－２α）治疗慢性丙型肝炎患者的疗效和安全性。方法 １８７例初治的慢性丙型肝炎（丙肝）患者,随机分成三组,分别接受：ＣＩＦＮ１５μｇ（Ａ组）６１例、９μｇ（Ｂ组）６５例和ＩＦＮα－２α３ＭＵ（Ｃ组）６１例,１周３次,共２４周,在完成治疗后继续随访２４周。本试验以治疗结束时和随访时丙氨     

Should aged patients with chronic hepatitis C be treated with interferon and ribavirin combination therapy?

The aim of this study was to investigate the efficacy and safety of combination therapy of interferon and ribavirin for aged patients with chronic hepatitis C. METHODS: This study was conducted at Osaka University Hospital and institutions participating in the Osaka Liver Disease Study Group on 329 patients with chronic hepatitis C receiving interferon and ribavirin combination therapy (group A, under 60 year old, n=199; group B, 60-64 year old, n=64; group C, over 65 year old (mean age, 67.8+/-2.2 year old, n=66)). Of the 293 patients who were tested for HCV serotype and HCV viral loads, 215 had HCV-RNA with serotype 1 and high viral loads (1H) and the other 78 had HCV-RNA with serotype 2 or low viral loads (non-1H). RESULTS: In per-protocol analysis, the overall SVR rate of 1H patients was 28% (51/184). Among the 1H patients, the SVR rate was significantly lower in group C (16%) and group B (17%) than in group A (34%) (p<0.05). The overall SVR rate of non-1H patients was 85% (57/67). No significant difference was found in the SVR rate among group C (79%), group B (100%), and group A (84%). On the other hand, the discontinuance of both drugs due to side effects was 29% (19/66) in group C, 20% (13/64) in group B, and 11% (21/199) in group A, with the discontinuance rates being higher in the older group (p=0.002). CONCLUSIONS: In aged chronic hepatitis C patients, interferon and ribavirin combination therapy can be recommended for the non-1H patients who showed a high SVR rate of approximately 65%, but not for the 1H patients.