發(fā)布時(shí)間：2018-05-23 11:20

  本文選題：干擾素 + 利巴韋林��； 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：了解慢性丙型肝炎患者接受干擾素聯(lián)合利巴韋林抗病毒治療的療效和安全性，以及影響療效的因素。 方法：1.采用回顧性和前瞻性研究方法，收集廣西醫(yī)科大學(xué)第一附屬醫(yī)院感染性疾病科門(mén)診2010年7月～2012年8月符合入選標(biāo)準(zhǔn)的慢性丙型肝炎患者64例，收集患者人口學(xué)資料及感染途徑；2.所有患者均給予干擾素（包括長(zhǎng)效及短效干擾素）聯(lián)合利巴韋林治療48周，同時(shí)隨訪至患者停藥后24周（如果患者在停藥24周內(nèi)復(fù)發(fā)則隨訪至復(fù)發(fā)時(shí)間點(diǎn)）；檢測(cè)治療前、治療后4周、12周、24周、48周、停藥后4周、12周、24周患者的肝功能、血常規(guī)及HCV RNA等指標(biāo)。3.按干擾素類(lèi)型分為短效組及長(zhǎng)效組，比較兩組患者抗病毒治療后獲得RVR、EVR、SVR的差異，評(píng)價(jià)兩組患者接受抗病毒治療的療效；4.根據(jù)患者治療前HCV RNA載量分為高病毒載量組（HCV RNA≥8.0×105IU/ml）和低病毒載量組（HCV RNA＜8.0×105IU/ml），分析不同基因型及基線HCV RNA病毒載量對(duì)慢性丙型肝炎患者抗病毒療效的影響。 結(jié)果：1.入選的64例慢性丙型肝炎患者，完成48周療程及停藥24周隨訪的57例，因副作用退出2例，脫落5例，最后進(jìn)入研究的患者57例。2.進(jìn)入研究的57例患者中48例檢出病毒基因型，基因型分布如下:1b型25例占多數(shù)（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.在完成全部療程及停藥后24周隨訪的57例患者中，獲得RVR、EVR、SVR的比率分別為71.9%、96.5%、84.2%。按不同的干擾素SVR的比率分別為85.3%、97.1%、82.4%和52.2%、95.7%、87.0%，經(jīng)比較兩組除RVR差異有統(tǒng)計(jì)學(xué)意義外，EVR及SVR差異無(wú)統(tǒng)計(jì)學(xué)意義。4.基因型對(duì)療效的影響：在完成全部療程及停藥后24周隨訪的57例患者中，其中48例檢出病毒基因型，基因1型患者28例，獲得的RVR、EVR、SVR率分別為57.1%、92.9%、75.0%，，基因2、3型患者10例，獲得的RVR、EVR、SVR率分別為80.0%、100.0%、90.0%，基因6型患者10例，獲得RVR、EVR、SVR率分別為90.0%、100.0%、100.0%。三種基因型間兩兩比較差異均無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.0167）。5.基因型、不同干擾素類(lèi)型對(duì)治療的影響：基因1型患者在重組干擾素α-2b聯(lián)合利巴韋林和聚乙二醇干擾素α-2a聯(lián)合利巴韋林抗病毒治療中獲得的RVR、EVR及SVR率分別為76.9%、92.3%、76.9%和40.0%、93.3%、80.0%，比較基因1型在兩組中獲得的RVR率、EVR率及SVR率，P值均大于0.05，差異無(wú)統(tǒng)計(jì)學(xué)意義。在非基因1型患者中，基因2、3型患者在重組干擾素α-2b組和聚乙二醇干擾素α-2a組獲得的RVR、EVR及SVR率分別為83.3%、100.0%、83.3%和75.0%、100.0%、100.0%；基因6型患者在重組干擾素α-2b組和聚乙二醇干擾素α-2a組獲得的RVR率、EVR率及SVR率分別為100.0%、100.0%、100.0%和50%、100.0%、100.0%；基因2、3型及基因6型在兩組不同類(lèi)型干擾素抗病毒治療中的RVR、EVR及SVR率比較，P值均大于0.05，差異無(wú)統(tǒng)計(jì)學(xué)意義。6.HCV RNA病毒載量、不同干擾素類(lèi)型對(duì)治療的影響：在高病毒載量組（HCV RNA≥8.0×105IU/ml）中，重組干擾素α-2b組和聚乙二醇干擾素α-2a組獲得的RVR、EVR、SVR率分別為85.7%、85.7%、85.7%和30.0%、90.0%、70.0%。兩組RVR率、EVR率及SVR率獲得比較，P值均大于0.05，差異無(wú)統(tǒng)計(jì)學(xué)意義。在低病毒載量組（HCV RNA＜8.0×105IU/ml）中，重組干擾素α-2b組和聚乙二醇干擾素α-2a組獲得的RVR率、EVR率、SVR率分別為85.2%、96.3%、81.5%和69.2%、100.0%、100.0%，兩組間比較差異無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）。7.未獲得SVR患者的情況分析：在完成全程聯(lián)合治療及24周隨訪的患者中有9例出現(xiàn)復(fù)發(fā)，其中6例未獲得RVR，5例（83.3%）為基因1型，1例（16.7%）為基因3型；高低病毒載量組各3例（50.0%）；短效及長(zhǎng)效干擾素組分別為4例（66.7%）和2例（33.3%）；另3例獲得RVR及EVR者仍出現(xiàn)復(fù)發(fā)，2例為基因1型，1例未分型。重組干擾素α-2b組和聚乙二醇干擾素α-2a組復(fù)發(fā)例數(shù)分別為6例（6/34,17.7%）和3例（3/23,13.0%）；HCV基因1型28例復(fù)發(fā)7例（7/28，25.0%）和非基因1型20例復(fù)發(fā)1例,(1/20,5.0%）1例未分型患者復(fù)發(fā)；高、低病毒載量組復(fù)發(fā)率分別為4例（4/17,23.5%）和5例（5/40,12.5%），結(jié)果提示未獲得RVR者復(fù)發(fā)率較RVR者顯著升高，兩者差異有統(tǒng)計(jì)學(xué)意義，其次為基因1型和高病毒載量組復(fù)發(fā)率較高，但上述干擾素類(lèi)型、基因型及病毒載量組間復(fù)發(fā)率比較，P＞0.05,差異無(wú)統(tǒng)計(jì)學(xué)意義。8.兩組患者治療過(guò)程中出現(xiàn)的不良事件均為干擾素常見(jiàn)的不良反應(yīng)，兩組不良事件發(fā)生率相似。聚乙二醇干擾素α-2a組有8例因中性粒細(xì)胞低于0.75×109/L而減量為135ug/周，而重組干擾素α-2b組有4例減量（P值為0.078）。短效組和長(zhǎng)效組分別有3例和6例因輕度貧血(Hb＜100g/L)將利巴韋林減量為600mg/d（P值為0.167）。甲狀腺功能異常在重組干擾素α-2b組發(fā)生率（22.6%）明顯高于聚乙二醇干擾素α-2a組（4%），但兩者差異無(wú)統(tǒng)計(jì)學(xué)意義（P值為0.178）。 結(jié)論：1.慢性丙型肝炎患者接受干擾素聯(lián)合利巴韋林抗病毒治療48周有84.2%獲得SVR。 2.基因1型與非基因1型的患者SVR率分別為75.0%和95.0%(基因2、3型為90%,基因6型為100%)。 3.重組干擾素α-2b與聚乙二醇干擾素α-2a聯(lián)合利巴韋林兩組患者獲得SVR率無(wú)差別，安全性好。 4.病毒載量水平高低不影響慢性丙型肝炎患者抗病毒治療的SVR率。 5.國(guó)內(nèi)外的RGT治療均是以長(zhǎng)效干擾素為基礎(chǔ)的，對(duì)于短效干擾素治療無(wú)RGT治療方案，對(duì)于基因1型及高病毒載量組的慢性丙型肝炎患者應(yīng)用短效干擾素治療盡管獲得RVR，仍需延長(zhǎng)治療療程來(lái)提高SVR率及降低復(fù)發(fā)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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R512.63

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