發(fā)布時(shí)間：2018-02-28 19:36

  本文關(guān)鍵詞： 乙肝患者 核苷酸(酸)類似物 管理 治療 轉(zhuǎn)歸　出處：《廣西醫(yī)科大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：目的探討長期核苷(酸)類似物(Nucleos(t)ide analogues, NAs)治療與綜合管理對慢性乙型肝炎病毒(Hepatitis B virus,HBV)感染者的臨床轉(zhuǎn)歸。 方法建立慢性乙型病毒性肝炎(CHB)、肝硬化(LC)、HBV相關(guān)肝癌術(shù)后和肝移植術(shù)后患者Nas抗病毒治療隊(duì)列。通過定期隨訪、監(jiān)控相關(guān)指標(biāo),及早發(fā)現(xiàn)耐藥、復(fù)發(fā),及時(shí)調(diào)整治療方案,最大限度抑制HBVDNA,穩(wěn)定肝功能。應(yīng)用生存分析方法計(jì)算患者進(jìn)入隊(duì)列至末次訪視日期的臨床終點(diǎn)事件(肝硬化、肝癌、肝癌復(fù)發(fā)、肝移植術(shù)后乙肝復(fù)發(fā))累積發(fā)生率及年發(fā)生率,并用COX風(fēng)險(xiǎn)模型分析影響CHB/LC患者肝硬化、肝癌發(fā)生的危險(xiǎn)因素。觀察隨訪隊(duì)列中CHB合并妊娠患者母嬰阻斷及母嬰健康情況。 結(jié)果(1)705例CHB、LC患者,平均隨訪4.0年(1.0年～11.4年),至末次訪視,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%)發(fā)生肝硬化,5例(0.9%)發(fā)生肝癌,5年累積發(fā)生率分別為8.0%及3.3%,年發(fā)生率分別為0.6及0.2%。LC患者154例,14例(9.1%)發(fā)生肝癌,5年累積發(fā)生率為14.3%,年發(fā)生率2.4%。代償期LC患者114例,7例(6.2%)發(fā)生肝癌,2例(1.8%)發(fā)生失代償。失代償期患者40例,5例(12.5%)發(fā)生肝癌；4例(10%)死于上消化道大出血。COX比例風(fēng)險(xiǎn)模型分析顯示治療基線HBeAg陰性及年齡大是發(fā)生肝硬化的獨(dú)立危險(xiǎn)因素。肝硬化、經(jīng)治患者及基線HBeAg陰性是發(fā)生HCC的主要危險(xiǎn)因素,而年齡大、治療過程ALT反復(fù)波動(dòng)為次要危險(xiǎn)因素。 (2)HBV相關(guān)肝癌術(shù)后患者30例,平均隨訪2.4年(1個(gè)月～7.5年),肝癌復(fù)發(fā)5例(16.7%),年復(fù)發(fā)率7.7%。2例(6.7%)死于上消化道大出血,年病死率2.7%。 (3)HBV相關(guān)肝移植術(shù)后患者28例,平均隨訪3.8年(2個(gè)月～8年),5例(17.9%)出現(xiàn)HBV復(fù)發(fā),年復(fù)發(fā)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治療的CHB合并妊娠患者共36例。有4例尚在妊娠,1例在孕14周時(shí)發(fā)生流產(chǎn)(第二胎)。32例孕母已經(jīng)順產(chǎn)36個(gè)嬰兒(其中有3對雙胞胎,有1例孕母育2次),母嬰均平安。除1例患兒確診先天性心臟病(有先心家族史)外,另35例嬰兒發(fā)育正常,其中31例嬰兒在出生后1-12個(gè)月測靜脈血HBV-DNA/HBsAg均陰性。 上述相關(guān)終點(diǎn)事件的累積發(fā)生率及年發(fā)生率均低于文獻(xiàn)自然史進(jìn)展報(bào)道。 結(jié)論長期規(guī)范的核苷(酸)類似物治療與綜合管理相結(jié)合,能夠最大限度抑制病毒復(fù)制,維持患者肝功能處于穩(wěn)定狀態(tài),從而降低肝硬化、肝癌的發(fā)生率、肝癌復(fù)發(fā)率、肝移植患者HBV復(fù)發(fā)率,減少母嬰傳播及保護(hù)母嬰健康。治療基線HBeAg陰性及年齡大是發(fā)生肝硬化獨(dú)立危險(xiǎn)因素,而基線HbeAg陰性、經(jīng)治患者及肝硬化是發(fā)生肝癌獨(dú)立危險(xiǎn)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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.62

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