發(fā)布時間：2018-03-31 02:07

  本文選題：慢性丙型肝炎　切入點：隊列研究　出處：《南方醫(yī)科大學(xué)》2017年博士論文

【摘要】：背景和目的慢性丙型肝炎(chronic hepatitis C,CHC)是一種由丙型肝炎病毒(hepatitis C virus,HCV)感染引起的病毒性肝炎。據(jù)世界衛(wèi)生組織統(tǒng)計,全球HCV感染率約為3%,估計約1.8億人感染了 HCV,且每年新發(fā)丙型肝炎病例約3.5萬。丙型肝炎呈全球性流行,可導(dǎo)致肝臟慢性炎癥壞死和纖維化,部分患者可發(fā)展為肝硬化甚至肝細(xì)胞癌(hepatocellular carcinoma,HCC)。未來20年內(nèi)與HCV感染相關(guān)的死亡率(肝衰竭和HCC導(dǎo)致的死亡)將繼續(xù)增加,對患者的健康和生命危害極大,已成為嚴(yán)重的社會和公共衛(wèi)生問題。PEG-干擾素聯(lián)合利巴韋林抗病毒是CHC的標(biāo)準(zhǔn)治療方案,其目的是阻止慢性丙肝進展為肝硬化、HCC或者死亡,最終提高患者的生活質(zhì)量。一般認(rèn)為,如果CHC患者經(jīng)標(biāo)準(zhǔn)方案抗病毒治療獲得持續(xù)病毒學(xué)應(yīng)答(sustained virological response,SVR),就可以認(rèn)為達到了臨床治愈,但是在停藥后的隨訪過程中,常常發(fā)現(xiàn)有的患者發(fā)生了病毒學(xué)復(fù)發(fā),因此,我們認(rèn)為,獲得SVR僅僅是實現(xiàn)了慢性丙肝長期抗病毒治療目標(biāo)的第一步。慢性丙肝患者實現(xiàn)SVR后的短期獲益已經(jīng)非常明確,但是人們對于獲得SVR后的長期獲益(臨床的、生化學(xué)的、病毒學(xué)的和組織學(xué)的)知之甚少。尤其是,要實現(xiàn)慢性丙肝抗病毒治療的最終目標(biāo),往往需要數(shù)年甚至數(shù)十年的觀察研究才能完成。而現(xiàn)有的少數(shù)幾項長期隨訪研究因納入患者數(shù)量較少、隨訪時間較短、治療方案不同、缺少組織學(xué)評價或組織樣本量太少等使得研究結(jié)果缺乏可靠性。因此,我們極有必要進行一項長期的大規(guī)模的隊列研究,以準(zhǔn)確評價慢性丙肝患者獲得SVR后的臨床、生化、病毒學(xué)和組織學(xué)結(jié)果。方法在2002年至2015年間,我們在中國5家醫(yī)療中心納入325例獲得SVR的慢性丙肝患者,進行中位隨訪時間為10年的前瞻性隊列研究,以評估其臨床結(jié)局及其影響因素。結(jié)果隨訪結(jié)束時,5人發(fā)展為失代償期肝硬化,1人確診為HCC,2人死于肝臟相關(guān)疾病(HCC、肝硬化)。305人的ALT和AST水平在隨訪期內(nèi)始終正常,27人發(fā)生了病毒復(fù)發(fā)。117人接受了二次肝活檢,96人的纖維化程度改善,99人的炎癥評分下降,37人的肝組織結(jié)構(gòu)正�；蚪咏�。結(jié)論慢性丙肝患者經(jīng)PEG-干擾素聯(lián)合利巴韋林治療獲得的SVR是持久的,但是少數(shù)患者會有病毒復(fù)學(xué)發(fā)�；颊叩呐R床結(jié)局是良好的,但是極少數(shù)患者在獲得SVR后仍然有發(fā)生HCC的風(fēng)險。經(jīng)多重邏輯回歸分析發(fā)現(xiàn),年齡、基因型、纖維化程度和RVR或EVR的出現(xiàn)是病毒學(xué)復(fù)發(fā)的獨立預(yù)測因子。
[Abstract]:Background and objective chronic hepatitis C (hepatitis) is a viral hepatitis caused by hepatitis C virus (hepatitis C virus) infection. The global infection rate of HCV is estimated to be about 180 million, and the annual number of new cases of hepatitis C is about 35000. Hepatitis C is a global epidemic that can lead to chronic inflammation, necrosis and fibrosis of the liver. Some patients may develop into liver cirrhosis or even hepatocellular carcinoma. The mortality associated with HCV infection (liver failure and death caused by HCC) will continue to increase in the next 20 years, which is extremely harmful to the health and life of patients. Has become a serious social and public health problem. PEG- interferon combined with ribavirin is the standard treatment for CHC, which is designed to prevent the progression or death of chronic hepatitis C to cirrhosis, and ultimately to improve the quality of life of patients. If patients with CHC receive sustained virological response via standard antiviral therapy, they can be considered to be clinically cured. However, during follow-up after withdrawal of the drug, some patients are often found to have relapsed virology. In our opinion, getting SVR is only the first step in achieving the goal of long-term antiviral therapy for chronic hepatitis C. the short-term benefits of SVR in patients with chronic hepatitis C are very clear, but the long-term benefits of obtaining SVR (clinically, Little is known about biochemistry, virology and histology. In particular, the ultimate goal of antiviral therapy for chronic hepatitis C is to be achieved. It often takes years or even decades of observational studies to complete, while the few existing long-term follow-up studies include fewer patients, shorter follow-up periods and different treatment options. The lack of histological evaluation or too few tissue samples makes the results of the study less reliable. Therefore, it is extremely necessary to conduct a long-term, large-scale cohort study to accurately evaluate the clinical, biochemical characteristics of patients with chronic hepatitis C after obtaining SVR. Methods from 2002 to 2015, we enrolled 325 chronic hepatitis C patients with SVR in 5 medical centers in China. A prospective cohort study with a median follow-up time of 10 years was conducted. Results at the end of the follow-up period, 5 patients developed into decompensated cirrhosis and 1 patient died of liver related diseases. The levels of ALT and AST remained normal during the follow-up period. The degree of fibrosis was improved in 96 patients with secondary liver biopsy. The inflammation score of 99 patients decreased. The liver tissue structure of 37 patients with chronic hepatitis C was normal or close to normal. Conclusion the patients with chronic hepatitis C were treated with PEG- interferon combined therapy. SVR obtained by Bavirin therapy is persistent. But a few patients have a relapse of the virus. The clinical outcome of the patients is good, but a very small number of patients are still at risk of developing HCC after obtaining SVR. Multiple logistic regression analysis shows that age, genotype, The degree of fibrosis and the presence of RVR or EVR are independent predictors of the recurrence of virology.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R512.63

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