经peg-干扰素联合利巴韦林治疗获得持续病毒学应答的慢性丙肝患者十年随访结果及其预测因素分析

发布时间：2018-03-31 02:07

本文选题：慢性丙型肝炎　切入点：队列研究　出处：《南方医科大学》2017年博士论文

【摘要】：背景和目的慢性丙型肝炎(chronic hepatitis C,CHC)是一种由丙型肝炎病毒(hepatitis C virus,HCV)感染引起的病毒性肝炎。据世界卫生组织统计,全球HCV感染率约为3%,估计约1.8亿人感染了 HCV,且每年新发丙型肝炎病例约3.5万。丙型肝炎呈全球性流行,可导致肝脏慢性炎症坏死和纤维化,部分患者可发展为肝硬化甚至肝细胞癌(hepatocellular carcinoma,HCC)。未来20年内与HCV感染相关的死亡率(肝衰竭和HCC导致的死亡)将继续增加,对患者的健康和生命危害极大,已成为严重的社会和公共卫生问题。PEG-干扰素联合利巴韦林抗病毒是CHC的标准治疗方案,其目的是阻止慢性丙肝进展为肝硬化、HCC或者死亡,最终提高患者的生活质量。一般认为,如果CHC患者经标准方案抗病毒治疗获得持续病毒学应答(sustained virological response,SVR),就可以认为达到了临床治愈,但是在停药后的随访过程中,常常发现有的患者发生了病毒学复发,因此,我们认为,获得SVR仅仅是实现了慢性丙肝长期抗病毒治疗目标的第一步。慢性丙肝患者实现SVR后的短期获益已经非常明确,但是人们对于获得SVR后的长期获益(临床的、生化学的、病毒学的和组织学的)知之甚少。尤其是,要实现慢性丙肝抗病毒治疗的最终目标,往往需要数年甚至数十年的观察研究才能完成。而现有的少数几项长期随访研究因纳入患者数量较少、随访时间较短、治疗方案不同、缺少组织学评价或组织样本量太少等使得研究结果缺乏可靠性。因此,我们极有必要进行一项长期的大规模的队列研究,以准确评价慢性丙肝患者获得SVR后的临床、生化、病毒学和组织学结果。方法在2002年至2015年间,我们在中国5家医疗中心纳入325例获得SVR的慢性丙肝患者,进行中位随访时间为10年的前瞻性队列研究,以评估其临床结局及其影响因素。结果随访结束时,5人发展为失代偿期肝硬化,1人确诊为HCC,2人死于肝脏相关疾病(HCC、肝硬化)。305人的ALT和AST水平在随访期内始终正常,27人发生了病毒复发。117人接受了二次肝活检,96人的纤维化程度改善,99人的炎症评分下降,37人的肝组织结构正常或接近正常。结论慢性丙肝患者经PEG-干扰素联合利巴韦林治疗获得的SVR是持久的,但是少数患者会有病毒复学发。患者的临床结局是良好的,但是极少数患者在获得SVR后仍然有发生HCC的风险。经多重逻辑回归分析发现,年龄、基因型、纤维化程度和RVR或EVR的出现是病毒学复发的独立预测因子。
[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.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R512.63

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