本文選題：丙型肝炎病毒 + 直接抗病毒藥物　； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:近日,世界衛(wèi)生組織(World Health Organization,WHO)提出了“到2030年消除病毒性肝炎作為公共健康威脅”的全球肝炎防治策略。直接抗病毒藥物(Direct-acting antiviral agents,DAAs)的問(wèn)世使得丙型肝炎病毒(Hepatitis C Virus,HCV)感染的防治似乎更容易達(dá)到目標(biāo)。但DAAs耐藥相關(guān)變異(Resistance-associated variants,RAVs)的出現(xiàn)會(huì)降低DAAs治療的效果,甚至導(dǎo)致治療失敗。然而全球HCV DAAs的預(yù)存耐藥流行情況還不清楚。此外,我國(guó)作為肝炎大國(guó),目前HCV感染的流行和治療情況也不清楚。因此,了解清楚上述問(wèn)題對(duì)早日實(shí)現(xiàn)WHO提出的宏偉目標(biāo)來(lái)說(shuō)是很有必要的。方法:1.全球HCV直接抗病毒藥物預(yù)存耐藥突變流行情況分析:首先從NCBI Gen Bank核酸數(shù)據(jù)庫(kù)提取所有的HCV全長(zhǎng)序列。其次,查閱文獻(xiàn),總結(jié)出所有已知的DAAs耐藥突變位點(diǎn)(包括臨床相關(guān)的耐藥位點(diǎn))。再用MEGA 5.0軟件比對(duì)所得序列,分析其耐藥突變位點(diǎn)的流行情況。最后用SPSS 20.0軟件統(tǒng)計(jì)結(jié)果。2.中國(guó)西部HCV感染的流行及治療情況分析:我們回顧性的分析了2013-2015年在我院檢測(cè)HCV抗體(Antibody,Ab)的病人的電子病歷。分析了HCV-Ab的陽(yáng)性率以及HCV-RNA陽(yáng)性病人的治療情況。用SPSS 20.0軟件統(tǒng)計(jì)結(jié)果。結(jié)果:1.總的來(lái)說(shuō),全球HCV DAAs預(yù)存耐藥突變流行率是很高的(58.7%,854/1455)。在各大洲中,DAAs預(yù)存耐藥突變流行率最高的是亞洲(74.1%),其次是非洲(71.9%),美洲(53.5%)和歐洲(51.4%)。在各個(gè)基因型中,基因6型的預(yù)存耐藥突變率是最高的(99%),接下來(lái)是基因4型,基因1a型,基因3型和基因1b型(分別是85.5%,56%,50%和34.3%)。對(duì)于不同種類的DAAs而言,我們發(fā)現(xiàn)有40.0%的序列含有針對(duì)NS5A抑制劑的RAVs;29.6%的序列含有針對(duì)NS3蛋白酶抑制劑的RAVs。值得注意的是,針對(duì)NS5B核苷酸抑制劑(Nucleotide inhibitor,NI)的RAVs是罕見的(4%的序列)。同時(shí)正如我們預(yù)期的那樣,對(duì)于目前各大指南推薦的無(wú)干擾素治療方案的聯(lián)合耐藥突變率是非常低的(0.2-2.0%)。2.總的來(lái)說(shuō),HCV-Ab的陽(yáng)性率是1.44%(1616/112576)。男性的HCV-Ab陽(yáng)性率要高于女性(1.96%比1.06%,p0.01)。35-44年齡組的HCV-Ab陽(yáng)性率是最高的(3.24%,591/18254)。而非感染科來(lái)源的病人的HCV-Ab陽(yáng)性率是0.64%(634/99061)。此外,在1616個(gè)HCV-Ab陽(yáng)性的患者中,有1278(79.08%)名患者接受了HCV-RNA檢測(cè),其中有951(74.41%)名患者是HCV-RNA陽(yáng)性。值得注意的是,在這些HCV-RNA陽(yáng)性的患者中,只有45.64%(434/951)的患者接受了標(biāo)準(zhǔn)的聚乙二醇干擾素聯(lián)合利巴韋林(Peg-IFN/Ribavirin,P/R)治療。但是接受治療的HCV感染患者的治愈率還是很高的(73.51%,272/370)。此外,有10.96%(32/292)的HCV-RNA陽(yáng)性患者同時(shí)也檢測(cè)到了HBs Ag陽(yáng)性。這32名患者的HCV治愈率比HBs Ag陰性患者低,但沒(méi)有統(tǒng)計(jì)學(xué)差異。結(jié)論:1.全球HCV DAAs預(yù)存耐藥突變的流行率是很高的,無(wú)論是在各大洲還是各基因型。但是,以NI為基礎(chǔ)的DAAs聯(lián)合方案的耐藥突變流行率是很低的,提示我們這些治療方案可能是治療慢性丙型肝炎較好的策略。2.我國(guó)的HCV感染患者可能自2006年HCV感染人口普查以來(lái)有所增加。P/R治療方案在我國(guó)的治愈率還是很高的,但是仍有一半以上的患者沒(méi)有接受治療。因此,更加科學(xué)、全面、合理的HCV感染防治策略的制定和實(shí)施是很有必要的。
[Abstract]:Objective: Recently, the WHO (World Health Organization, WHO) proposed a global hepatitis control strategy to eliminate viral hepatitis as a public health threat. The advent of the direct antiviral drug (Direct-acting antiviral agents, DAAs) makes the prevention and control of hepatitis C virus (Hepatitis C Virus, HCV) infection more likely. It is easy to achieve the goal. However, the emergence of DAAs resistance related variants (Resistance-associated variants, RAVs) can reduce the effect of DAAs treatment and even lead to treatment failure. However, the prevalence of HCV DAAs in the global HCV DAAs is not clear. In addition, our country is a major hepatitis, and the prevalence and treatment of HCV infection is not clear. Therefore, it is not clear that the prevalence and treatment of HCV infection are not clear. It is necessary to clear the above problems for the early realization of the grand goal of WHO. Method: analysis of the epidemic situation of the 1. global HCV direct antiviral drugs. First, all HCV full-length sequences are extracted from the NCBI Gen Bank nucleic acid database. Secondly, all the known DAAs mutation sites (package) are summarized. MEGA 5 software alignment was used to analyze the prevalence of drug-resistant mutation sites. Finally, SPSS 20 software was used to analyze the prevalence and treatment of HCV infection in Western China: a retrospective analysis of 2013-2015 years in our hospital for the detection of HCV antibody (Antibody, Ab) patients in our hospital. The positive rate of HCV-Ab and the treatment of HCV-RNA positive patients were analyzed. The results of SPSS 20 software were used. Results: 1. overall, the global HCV DAAs preexisting resistance mutation prevalence rate was very high (58.7%, 854/1455). Among the continents, the highest prevalence rate of DAAs preexisting mutation was Asia (74.1%), followed by Africa (71.9%), beauty. Chau (53.5%) and Europe (51.4%). In various genotypes, the preexisting resistance mutation rate of gene 6 is the highest (99%), followed by gene 4, gene 1a, gene 3, and gene 1B (85.5%, 56%, 50% and 34.3% respectively). For different types of DAAs, we found that 40% sequences contain RAVs for NS5A inhibitors; 29.6% sequence It is noteworthy that the RAVs. for NS3 protease inhibitors is that the RAVs of the NS5B nucleotide inhibitor (Nucleotide inhibitor, NI) is a rare (4% sequence). And as we expected, the combined resistance mutation rate for interferon free treatments recommended by the major guidelines is very low (0.2-2.0%).2. total. The positive rate of HCV-Ab was 1.44% (1616/112576). The positive rate of HCV-Ab in men was higher than that in women (1.96% to 1.06%, P0.01) in.35-44 age group (3.24%, 591/18254). The HCV-Ab positive rate in non infectious patients was 0.64% (634/ 99061). In addition, among 1616 HCV-Ab positive patients, there were 1278 (79.08%) names. The patients received a HCV-RNA test, of which 951 (74.41%) were HCV-RNA positive. It is worth noting that only 45.64% (434/951) of the HCV-RNA positive patients received the standard peginterferon combined with Leigh Bhave Lin (Peg-IFN/Ribavirin, P/ R) treatment. But the cure rate of HCV infected patients received treatment was still still It was very high (73.51%, 272/370). In addition, 10.96% (32/292) HCV-RNA positive patients also detected HBs Ag positive. The HCV cure rate of these 32 patients was lower than that of HBs Ag negative patients, but there was no statistical difference. Conclusion: the prevalence rate of 1. global HCV DAAs predeposited mutations is very high, whether in all continents or genotypes. It is, the NI based DAAs combination regimen is very low in resistance mutation prevalence, suggesting that these treatments may be a better strategy for the treatment of chronic hepatitis C.2., our HCV infected patients may have increased the cure rate in our country since the 2006 HCV infection population census, but the cure rate in our country is still high, but still there is a high rate of cure in China. More than half of the patients did not receive treatment. Therefore, it is necessary to formulate and implement a more scientific, comprehensive and rational strategy for the prevention and treatment of HCV infection.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.63

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 Luigi E Adinolfi;Barbara Guerrera;;All-oral interferon-free treatments:The end of hepatitis C virus story,the dream and the reality[J];World Journal of Hepatology;2015年22期

2 Gaia Caccamo;Francesca Saffioti;Giovanni Raimondo;;Hepatitis B virus and hepatitis C virus dual infection[J];World Journal of Gastroenterology;2014年40期

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本文編號(hào)：1840995