干扰素联合利巴韦林治疗慢性丙型肝炎的疗效分析

发布时间：2018-05-23 11:20

本文选题：干扰素 + 利巴韦林　；参考：《广西医科大学》2014年硕士论文

【摘要】：目的：了解慢性丙型肝炎患者接受干扰素联合利巴韦林抗病毒治疗的疗效和安全性，以及影响疗效的因素。方法：1.采用回顾性和前瞻性研究方法，收集广西医科大学第一附属医院感染性疾病科门诊2010年7月～2012年8月符合入选标准的慢性丙型肝炎患者64例，收集患者人口学资料及感染途径；2.所有患者均给予干扰素（包括长效及短效干扰素）联合利巴韦林治疗48周，同时随访至患者停药后24周（如果患者在停药24周内复发则随访至复发时间点）；检测治疗前、治疗后4周、12周、24周、48周、停药后4周、12周、24周患者的肝功能、血常规及HCV RNA等指标。3.按干扰素类型分为短效组及长效组，比较两组患者抗病毒治疗后获得RVR、EVR、SVR的差异，评价两组患者接受抗病毒治疗的疗效；4.根据患者治疗前HCV RNA载量分为高病毒载量组（HCV RNA≥8.0×105IU/ml）和低病毒载量组（HCV RNA＜8.0×105IU/ml），分析不同基因型及基线HCV RNA病毒载量对慢性丙型肝炎患者抗病毒疗效的影响。结果：1.入选的64例慢性丙型肝炎患者，完成48周疗程及停药24周随访的57例，因副作用退出2例，脱落5例，最后进入研究的患者57例。2.进入研究的57例患者中48例检出病毒基因型，基因型分布如下:1b型25例占多数（52.1%),其次是6a型10例(20.8%),3b型6例（12.5%），2a型4例（8.3%)和1a型3例（6.3%)。3.在完成全部疗程及停药后24周随访的57例患者中，获得RVR、EVR、SVR的比率分别为71.9%、96.5%、84.2%。按不同的干扰素SVR的比率分别为85.3%、97.1%、82.4%和52.2%、95.7%、87.0%，经比较两组除RVR差异有统计学意义外，EVR及SVR差异无统计学意义。4.基因型对疗效的影响：在完成全部疗程及停药后24周随访的57例患者中，其中48例检出病毒基因型，基因1型患者28例，获得的RVR、EVR、SVR率分别为57.1%、92.9%、75.0%，，基因2、3型患者10例，获得的RVR、EVR、SVR率分别为80.0%、100.0%、90.0%，基因6型患者10例，获得RVR、EVR、SVR率分别为90.0%、100.0%、100.0%。三种基因型间两两比较差异均无统计学意义（P＞0.0167）。5.基因型、不同干扰素类型对治疗的影响：基因1型患者在重组干扰素α-2b联合利巴韦林和聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗中获得的RVR、EVR及SVR率分别为76.9%、92.3%、76.9%和40.0%、93.3%、80.0%，比较基因1型在两组中获得的RVR率、EVR率及SVR率，P值均大于0.05，差异无统计学意义。在非基因1型患者中，基因2、3型患者在重组干扰素α-2b组和聚乙二醇干扰素α-2a组获得的RVR、EVR及SVR率分别为83.3%、100.0%、83.3%和75.0%、100.0%、100.0%；基因6型患者在重组干扰素α-2b组和聚乙二醇干扰素α-2a组获得的RVR率、EVR率及SVR率分别为100.0%、100.0%、100.0%和50%、100.0%、100.0%；基因2、3型及基因6型在两组不同类型干扰素抗病毒治疗中的RVR、EVR及SVR率比较，P值均大于0.05，差异无统计学意义。6.HCV RNA病毒载量、不同干扰素类型对治疗的影响：在高病毒载量组（HCV RNA≥8.0×105IU/ml）中，重组干扰素α-2b组和聚乙二醇干扰素α-2a组获得的RVR、EVR、SVR率分别为85.7%、85.7%、85.7%和30.0%、90.0%、70.0%。两组RVR率、EVR率及SVR率获得比较，P值均大于0.05，差异无统计学意义。在低病毒载量组（HCV RNA＜8.0×105IU/ml）中，重组干扰素α-2b组和聚乙二醇干扰素α-2a组获得的RVR率、EVR率、SVR率分别为85.2%、96.3%、81.5%和69.2%、100.0%、100.0%，两组间比较差异无统计学意义（P＞0.05）。7.未获得SVR患者的情况分析：在完成全程联合治疗及24周随访的患者中有9例出现复发，其中6例未获得RVR，5例（83.3%）为基因1型，1例（16.7%）为基因3型；高低病毒载量组各3例（50.0%）；短效及长效干扰素组分别为4例（66.7%）和2例（33.3%）；另3例获得RVR及EVR者仍出现复发，2例为基因1型，1例未分型。重组干扰素α-2b组和聚乙二醇干扰素α-2a组复发例数分别为6例（6/34,17.7%）和3例（3/23,13.0%）；HCV基因1型28例复发7例（7/28，25.0%）和非基因1型20例复发1例,(1/20,5.0%）1例未分型患者复发；高、低病毒载量组复发率分别为4例（4/17,23.5%）和5例（5/40,12.5%），结果提示未获得RVR者复发率较RVR者显著升高，两者差异有统计学意义，其次为基因1型和高病毒载量组复发率较高，但上述干扰素类型、基因型及病毒载量组间复发率比较，P＞0.05,差异无统计学意义。8.两组患者治疗过程中出现的不良事件均为干扰素常见的不良反应，两组不良事件发生率相似。聚乙二醇干扰素α-2a组有8例因中性粒细胞低于0.75×109/L而减量为135ug/周，而重组干扰素α-2b组有4例减量（P值为0.078）。短效组和长效组分别有3例和6例因轻度贫血(Hb＜100g/L)将利巴韦林减量为600mg/d（P值为0.167）。甲状腺功能异常在重组干扰素α-2b组发生率（22.6%）明显高于聚乙二醇干扰素α-2a组（4%），但两者差异无统计学意义（P值为0.178）。结论：1.慢性丙型肝炎患者接受干扰素联合利巴韦林抗病毒治疗48周有84.2%获得SVR。 2.基因1型与非基因1型的患者SVR率分别为75.0%和95.0%(基因2、3型为90%,基因6型为100%)。 3.重组干扰素α-2b与聚乙二醇干扰素α-2a联合利巴韦林两组患者获得SVR率无差别，安全性好。 4.病毒载量水平高低不影响慢性丙型肝炎患者抗病毒治疗的SVR率。 5.国内外的RGT治疗均是以长效干扰素为基础的，对于短效干扰素治疗无RGT治疗方案，对于基因1型及高病毒载量组的慢性丙型肝炎患者应用短效干扰素治疗尽管获得RVR，仍需延长治疗疗程来提高SVR率及降低复发率。
[Abstract]:Objective: To investigate the efficacy and safety of interferon plus ribavirin in the treatment of chronic hepatitis C patients and the factors influencing the efficacy.
Methods: 1. a retrospective and prospective study was used to collect 64 cases of chronic hepatitis C in the outpatient department of infectious diseases in the First Affiliated Hospital of Guangxi Medical University from July 2010 to August 2012. The demographic data and the way of infection were collected, and 2. of the patients were given interferon (including long and short effect interference). Combined with Leigh Bhave Lin for 48 weeks, the patients were followed up to 24 weeks after stopping the drug (if the patient had a relapse in 24 weeks for 24 weeks). Before the treatment, 4 weeks, 12 weeks, 24 weeks, 48 weeks after the treatment, the liver function, blood routine and HCV RNA index were divided into short and long groups according to the type of interferon, and the indexes of.3. were divided into short effect group and length according to the interferon type. The difference of RVR, EVR, SVR after antiviral treatment in the two groups was compared, and the efficacy of two groups of patients received antiviral therapy was evaluated. 4. according to the HCV RNA load before treatment, the patients were divided into the high viral load group (HCV RNA > 8 x 105IU/ml) and the low viral load group (HCV RNA < 8 x 105IU/ml), and analyzed the different genotypes and the baseline HCV. Effect of dose on antiviral efficacy in patients with chronic hepatitis C.
Results: 1. of the 64 patients with chronic hepatitis C were enrolled in 57 cases of 48 weeks of treatment and 24 weeks' follow-up. 2 cases were exited due to side effects and 5 cases were dropped, and 57 cases of.2. entered the study. 48 cases were detected in the 57 patients. The genotype distribution was as follows: 1b type 25 accounted for majority (52.1%), followed by 6 6 10 cases, 3b Of 6 cases (12.5%), type 2A 4 cases (8.3%) and type 1A 3 cases (6.3%).3. in 57 patients who had completed the whole course of treatment and 24 weeks after the stop medicine, the ratio of RVR, EVR, and SVR was 71.9%, 96.5%, and 84.2%., respectively, was 85.3%, 97.1%, 82.4% and 52.2% respectively, EVR, respectively, EVR, except RVR differences were statistically significant, EVR. There was no statistically significant difference in the effect of the.4. genotype on the effect of SVR: of the 57 patients who had completed the whole course of treatment and 24 weeks after the withdrawal, 48 of them detected the virus genotypes and 28 patients with genotype 1. The rate of RVR, EVR, and SVR was 57.1%, 92.9%, 75%, and 10 of the gene 2,3 patients, and the RVR, EVR, and SVR rates were 80%, 100%, respectively. 90%, in 10 patients with genotype 6, RVR, EVR, and SVR rates were 90%, 100%, and 22 of 100.0%. three genotypes were not statistically significant (P > 0.0167).5. genotypes, and the effects of different interferon types on the treatment were: recombinant interferon alpha -2b combined with Leigh Bhave Lin and peginterferon alpha -2a combined with RIBA. The RVR, EVR and SVR rates were 76.9%, 92.3%, 76.9% and 40%, 93.3%, 80%, respectively. The RVR rate, EVR rate and SVR rate of the comparison gene 1 in the two groups were more than 0.05, and the difference was not statistically significant. In the non gene 1 patients, the gene 2,3 type patients were in the recombinant interferon a -2b group and peginterferon interferon alpha -2a. The rates of RVR, EVR and SVR obtained in the group were 83.3%, 100%, 83.3% and 75%, 100%, 100%, and the RVR rate obtained in the recombinant interferon alpha -2b group and the peginterferon alpha -2a group was 100%, 100%, 100% and 50%, 100%, 100%, and gene 2,3 type and gene 6 in different types of interferon resistance in the group. Compared with the rate of RVR, EVR and SVR in the drug treatment, the P values were all greater than 0.05, and there was no significant difference in.6.HCV RNA viral load and the effect of different interferon types on the treatment. In the high viral load group (HCV RNA > 8 x 105IU/ml), the recombinant interferon alpha -2b group and the polyethylene glycol interferon alpha -2a group were 85.7%, 85.7%, 85.7% respectively. The RVR rate, EVR rate and SVR rate of 30%, 90%, 70.0%. two groups were compared, P values were all greater than 0.05, and there was no statistical difference. In the low viral load group (HCV RNA < 8 x 105IU/ml), the RVR rate of recombinant interferon alpha -2b group and peginterferon alpha -2a group was obtained, and EVR rates were 85.2%, 96.3%, 81.5% and 69.2%, 100%, 100%, two, respectively. No statistically significant difference (P > 0.05).7. was not obtained in SVR patients: 9 cases relapsed in complete combined treatment and 24 week follow-up, of which 6 had no RVR, 5 (83.3%) was gene 1, 1 (16.7%) was gene 3; each of high and low viral load groups (50%); short and long effect interferon groups, respectively. 4 cases (66.7%) and 2 cases (33.3%), the other 3 cases of RVR and EVR still recurred, 2 were gene 1, 1 undivided. The recurrence rate of recombinant interferon alpha -2b group and peginterferon alpha -2a group were 6 (6/34,17.7%) and 3 cases (3/23,13.0%), HCV gene 1 28 recurrence 7 cases (7/28,25.0%) and non gene 1 relapse cases, (1/20,5.0) The recurrence rate of 1 undivided patients was 4 cases (4/17,23.5%) and 5 cases (5/40,12.5%), respectively. The results suggested that the recurrence rate of those who did not obtain RVR was significantly higher than those of the RVR, and the difference was statistically significant, followed by the high recurrence rate of gene 1 and HV load group, but the types of interferon, genotype and viral load were the following. The recurrence rate of the group was P > 0.05. The difference was not statistically significant in the.8. two group. All the adverse events in the treatment process were all interferon's common adverse reactions, and the incidence of two groups of adverse events was similar. 8 cases of peginterferon alpha -2a group were reduced to 135ug/ weeks because neutrophils were lower than 0.75 x 109 /L, and the recombinant interferon alpha -2b group was in the group of 135ug/. There were 4 cases of reduction (P value 0.078). There were 3 cases in short and long effect group and 6 cases with mild anemia (Hb < 100g/L) to reduce Leigh Bhave Lin to 600mg/d (P value 0.167). The incidence of thyroid dysfunction in recombinant interferon alpha -2b group (22.6%) was significantly higher than that of peginterferon alpha -2a group (4%), but there was no statistical difference between the two groups (P value 0.178).
Conclusion: 1. of patients with chronic hepatitis C received interferon plus ribavirin antiviral treatment for 48 weeks, and 84.2% received SVR..
The SVR rates of 2. genotype 1 and non genotype 1 were 75% and 95% (genotype 2,3 was 90%, and genotype 6 was 100%).
3. there was no difference in the SVR rate between the two groups of recombinant interferon alpha -2b and pegylated interferon alpha -2a plus ribavirin, and the safety was good.
4. the level of viral load does not affect the SVR rate of antiviral treatment in patients with chronic hepatitis C.
5. RGT treatment both at home and abroad is based on interferon, and there is no RGT therapy for interferon therapy. The use of short acting interferon (RVR) for chronic hepatitis C patients with gene 1 and HCV is still required to prolong the treatment course in order to increase the rate of SVR and reduce the recurrence rate.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.63

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