核苷（酸）类似物治疗与综合管理对慢性HBV感染者疾病转归的临床研究

发布时间：2018-02-28 19:36

本文关键词： 乙肝患者核苷酸(酸)类似物管理治疗转归　出处：《广西医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的探讨长期核苷(酸)类似物(Nucleos(t)ide analogues, NAs)治疗与综合管理对慢性乙型肝炎病毒(Hepatitis B virus,HBV)感染者的临床转归。方法建立慢性乙型病毒性肝炎(CHB)、肝硬化(LC)、HBV相关肝癌术后和肝移植术后患者Nas抗病毒治疗队列。通过定期随访、监控相关指标,及早发现耐药、复发,及时调整治疗方案,最大限度抑制HBVDNA,稳定肝功能。应用生存分析方法计算患者进入队列至末次访视日期的临床终点事件(肝硬化、肝癌、肝癌复发、肝移植术后乙肝复发)累积发生率及年发生率,并用COX风险模型分析影响CHB/LC患者肝硬化、肝癌发生的危险因素。观察随访队列中CHB合并妊娠患者母婴阻断及母婴健康情况。结果(1)705例CHB、LC患者,平均随访4.0年(1.0年～11.4年),至末次访视,91.1患者(642例)HBVDNA1000copy/mt88.4%患者(623例)ALT小于1.3倍正常下限(ULN)。CHB患者551例,14例(2.5%)发生肝硬化,5例(0.9%)发生肝癌,5年累积发生率分别为8.0%及3.3%,年发生率分别为0.6及0.2%。LC患者154例,14例(9.1%)发生肝癌,5年累积发生率为14.3%,年发生率2.4%。代偿期LC患者114例,7例(6.2%)发生肝癌,2例(1.8%)发生失代偿。失代偿期患者40例,5例(12.5%)发生肝癌；4例(10%)死于上消化道大出血。COX比例风险模型分析显示治疗基线HBeAg阴性及年龄大是发生肝硬化的独立危险因素。肝硬化、经治患者及基线HBeAg阴性是发生HCC的主要危险因素,而年龄大、治疗过程ALT反复波动为次要危险因素。 (2)HBV相关肝癌术后患者30例,平均随访2.4年(1个月～7.5年),肝癌复发5例(16.7%),年复发率7.7%。2例(6.7%)死于上消化道大出血,年病死率2.7%。 (3)HBV相关肝移植术后患者28例,平均随访3.8年(2个月～8年),5例(17.9%)出现HBV复发,年复发率4.8%。1例(3.6%)死于上消化道出血,年病死率0.9%。 (4)接受NAs治疗的CHB合并妊娠患者共36例。有4例尚在妊娠,1例在孕14周时发生流产(第二胎)。32例孕母已经顺产36个婴儿(其中有3对双胞胎,有1例孕母育2次),母婴均平安。除1例患儿确诊先天性心脏病(有先心家族史)外,另35例婴儿发育正常,其中31例婴儿在出生后1-12个月测静脉血HBV-DNA/HBsAg均阴性。上述相关终点事件的累积发生率及年发生率均低于文献自然史进展报道。结论长期规范的核苷(酸)类似物治疗与综合管理相结合,能够最大限度抑制病毒复制,维持患者肝功能处于稳定状态,从而降低肝硬化、肝癌的发生率、肝癌复发率、肝移植患者HBV复发率,减少母婴传播及保护母婴健康。治疗基线HBeAg阴性及年龄大是发生肝硬化独立危险因素,而基线HbeAg阴性、经治患者及肝硬化是发生肝癌独立危险因素。
[Abstract]:Objective to investigate the clinical outcome of chronic hepatitis B virus (HBV) infected patients treated with Nucleostidine analogues (NAs), a long term nucleoside analogue. Methods the Nas antiviral therapy cohort of patients with chronic viral hepatitis B (CHB), liver cirrhosis (LC) and HBV-associated liver cancer (HCC) after operation and after liver transplantation were established. Through regular follow up, monitoring of related indexes, early detection of drug resistance, recurrence, and timely adjustment of treatment regimen, Survival analysis was used to calculate the cumulative incidence and annual incidence of clinical endpoint events (liver cirrhosis, liver cancer, liver cancer recurrence, hepatitis B recurrence after liver transplantation) from the cohort to the date of the last visit. COX risk model was used to analyze the risk factors of liver cirrhosis and liver cancer in patients with CHB/LC, and the maternal and child block and maternal and child health of CHB complicated with pregnancy were observed in the follow-up cohort. Results 705 patients with CHBN LC, An average follow-up of 4.0 years (from 1.0 to 11.4 years, 642 patients with HBV DNA 1000 / mt88.4%) and 551 patients with alt less than 1.3 times the normal lower limit (14 / 2.5) developed liver cirrhosis in 5 (0.995%). The cumulative incidence in 5 years was 8.0% and 3.3%, respectively. The birth rates of 154 patients with LC were 0.6 and 0.2.LC (14 / 14 / 9. 1)) and the cumulative incidence for 5 years was 14. 3 and the annual incidence was 2. 4. 114 patients with compensatory LC (7 / 6. 2) developed liver cancer (2 / 1.8) and 40 patients with decompensated (5 / 12. 5) developed decompensation. Analysis of the proportional risk Model of death of Upper Gastrointestinal Hemorrhage (Cox) showed that baseline HBeAg negative and age were independent risk factors for liver cirrhosis. After treatment and baseline HBeAg negative is the main risk factor of HCC, but the age, the treatment process ALT repeatedly fluctuates as the secondary risk factor. 30 patients with HBV-associated liver cancer were followed up for an average of 2.4 years (from 1 month to 7.5 years after operation). The recurrence rate of liver cancer in 5 cases was 16.7%. The annual recurrence rate was 7.7.2 cases and 6.7%). The annual mortality rate was 2.7%. 28 patients with HBV-associated liver transplantation were followed up for an average of 3.8 years (ranging from 2 months to 8 years). The recurrence of HBV was found in 5 cases. The annual recurrence rate was 4.8.1 cases and 3.6 cases) died of upper gastrointestinal hemorrhage, and the annual mortality was 0.9%. 4) 36 cases of CHB complicated with pregnancy were treated with NAs. 4 cases were still pregnant and 1 case was aborted at the 14th week of gestation (second pregnancy, 32 cases, the mother had given birth to 36 babies (3 pairs of twins). Except for one case of congenital heart disease (congenital heart disease with family history), the other 35 cases had normal development, 31 of them were negative in venous blood HBV-DNA/HBsAg at 1-12 months after birth. The cumulative incidence and annual incidence of these related endpoint events were lower than those reported in the literature. Conclusion the combination of long-term standard nucleoside analogue therapy and comprehensive management can greatly inhibit viral replication and maintain a stable state of liver function in patients, thus reducing the incidence of liver cirrhosis, liver cancer, and the recurrence rate of liver cancer. The recurrence rate of HBV in patients with liver transplantation, the reduction of mother-to-child transmission and the protection of maternal and child health. Negative baseline HBeAg and age were independent risk factors for liver cirrhosis, while baseline HbeAg was negative, and treated patients and cirrhosis were independent risk factors for liver cancer.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62

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