慢性HBV感染者拉米夫定治療與全程管理的臨床轉(zhuǎn)歸研究
發(fā)布時(shí)間：2018-11-19 12:57
【摘要】：目的：探討慢性乙型肝炎患者長期拉米夫定治療與全程管理的臨床轉(zhuǎn)歸。 方法：本研究為回顧-前瞻性隊(duì)列研究。非隨機(jī)分為兩組：1)治療組：建立慢性乙型病毒性肝炎(CHB)和肝硬化(LC)的LAM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HBV DNA,穩(wěn)定肝功能。2)歷史對照組：從我科1990年以來門診和住院患者中篩選HBsAg陽性、ALT或AST異常、HBV-DNA陽性或HBeAg陽性、隨訪1年的未抗病毒治療患者共576例,通過傾向評分法(Propensity score method)按1：1匹配出與治療組一般資料(性別、年齡、基線E抗原、基線診斷)相近的265例作為歷史對照組。應(yīng)用生存分析方法計(jì)算兩組進(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、死亡)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。 結(jié)果：(1)治療組265例LAM治療CHB(79.6%)及LC患者,其中238(89.8%)例初治患者,男性占74.3%,基線E抗原陽性57.7%,平均年齡35.7±12歲。(2)歷史對照組265例,CHB(80%),74.3%男性,基線E抗原陽性59.2%,平均年齡35.7±12歲。至末次訪視,治療組和對照組HBV DNA1000copy/ml的患者比例分別為89.1%vs32.1%；兩組ALT小于1.3倍正常下限(ULN)的比例分別為89.8%vs18.5%。(3)治療組中87例(32.8%)曾出現(xiàn)病毒學(xué)突破,其中85例為拉米夫定耐藥,1、3、5年累積耐藥率6.1%、32.1%、38.9%,年均耐藥率為10.1%;另外2例為拉米夫定和阿德福韋酯共同耐藥；119例(44.9%)停藥,72例(60.5%)停藥后復(fù)發(fā),其中達(dá)《2010中國慢乙肝防治指南》停藥標(biāo)準(zhǔn)后停藥復(fù)發(fā)的有53.4%(39/73)例,未達(dá)標(biāo)停藥后復(fù)發(fā)率73.3%(33/45)。(4)治療組211例慢乙肝患者平均隨訪62±32月,8例發(fā)生肝硬化,3例發(fā)生肝癌,無死亡患者；對照組212例慢乙肝患者平均隨訪50±31月,83例發(fā)生肝硬化,9例發(fā)生肝癌,3例患者死亡；治療組與對照組慢乙肝患者3年、5年肝硬化累積發(fā)生率分別為0.6%vs13.8%,1.5%vs20.8%(P=0.000)；3年、5年肝癌累積發(fā)生率分別為0.0%vs2.6%,0.9%vs2.6%(P=0.11).治療組54例肝硬化患者平均隨訪5.2年(1.1年~11.6年),7例患者發(fā)生肝癌,1例患者死亡；對照組53例肝硬化患者平均隨訪3.4年(1.0年~16.4年),16例患者發(fā)生肝癌,3例發(fā)生乙肝相關(guān)性死亡；治療組和對照組3年、5年肝癌概率累計(jì)發(fā)生率分別為4.2%vs28.3%,10.7%vs39.3%(P=0.000),兩組3年、5年累積死亡率分別為0.6%vsl7.3%,2.4%vs22.5%(P=0.047)。(5) COX回歸分析顯示基線年齡大是發(fā)生肝硬化的獨(dú)立危險(xiǎn)因素�；�有肝硬化是發(fā)生HCC的獨(dú)立危險(xiǎn)因素。 結(jié)論：長期拉米夫定治療,部分人不可避免會出現(xiàn)耐藥、復(fù)發(fā),但只要規(guī)范的LAM治療與綜合管理相結(jié)合,就能夠長期最大限度抑制病毒復(fù)制,維持患者肝功能長期處于穩(wěn)定狀態(tài),降低肝硬化、肝癌的發(fā)生率及HBV相關(guān)性死亡率。治療基線年齡大是發(fā)生肝硬化獨(dú)立危險(xiǎn)因素,而基線診斷肝硬化是發(fā)生肝癌獨(dú)立危險(xiǎn)因素。
[Abstract]:Objective: to investigate the clinical outcome of long-term lamivudine therapy and whole-course management in patients with chronic hepatitis B. Methods: this study was a retrospective-prospective cohort study. Non-randomized groups were divided into two groups: 1) treatment group: to establish LAM antiviral therapy cohort of chronic hepatitis B (CHB) and liver cirrhosis (LC). Through regular follow-up, monitoring related indicators, early detection of drug resistance, recurrence, timely adjustment of treatment plan, maximum inhibition of HBV DNA, stable liver function. 2) Historical control group: screening positive HBsAg from outpatients and inpatients since 1990. 576 patients with abnormal ALT or AST, HBV-DNA positive or HBeAg positive, were followed up for one year without antiviral therapy. The general data (sex, age, baseline E antigen) of the treatment group (sex, age, baseline E antigen) were matched with the treatment group according to 1:1 by the tendency score method (Propensity score method). Baseline diagnosis) 265 cases were used as historical control group. Survival analysis was used to calculate the cumulative incidence and annual incidence of clinical endpoint events (cirrhosis, liver cancer, death) from the cohort to the date of the last visit. The COX risk model was used to analyze the effects of the two groups on liver cirrhosis in patients with CHB/LC. Risk factors for liver cancer. Results: (1) in the treatment group, 265 cases of CHB (79.6%) and LC were treated with LAM, of which 238 cases (89.8%) were newly treated, male accounted for 74.3%, and the baseline E antigen positive was 57.7%. The average age was 35.7 鹵12 years. (2) in the historical control group, there were 265 cases of, CHB (80%, 74.3% male, the baseline E antigen positive was 59.2 years old, the average age was 35.7 鹵12 years old. To the last visit, the proportion of HBV DNA1000copy/ml in the treatment group and the control group was 89.1vs32.1; (3) in the treatment group, 87 cases (32.8%) had virological breakthrough, 85 of them were lamivudine resistant, and 1 was 3, the ratio of ALT < 1.3 times normal lower limit (ULN) was 89.8vs18.5. (3) in the treatment group, 87 cases (32.8%) had a virological breakthrough, among which 85 cases were lamivudine resistant. The cumulative drug resistance rate in 5 years was 6.1% and 38.9%, and the average annual drug resistance rate was 10.1%. The other 2 cases were resistant to lamivudine and adefovir ester. One hundred and nineteen cases (44.9%) stopped drug withdrawal and 72 cases (60.5%) recurred after withdrawal. Among them, 53.4% (39 / 73) of the patients reached the standard of stopping drug withdrawal < 2010 Chinese guidelines for the prevention and treatment of chronic hepatitis B. The recurrence rate after discontinuation of drugs was 73.3% (33 / 45). (_ 4) in the treatment group. The mean follow-up of 211 patients with chronic hepatitis B was 62 鹵32 months. 8 cases had cirrhosis, 3 cases had liver cancer and no death. In the control group, 212 patients with chronic hepatitis B were followed up for an average of 50 鹵31 months, 83 patients developed cirrhosis, 9 patients developed liver cancer and 3 patients died. The cumulative incidence of liver cirrhosis in the treatment group and the control group for 3 years and 5 years was 0.6 vs 13.8and 1.5 vs 20.8% (P < 0.000). The cumulative incidence of liver cancer in 3 years and 5 years was 0. 0 vs 2. 6% and 0. 9% vs 2. 6% (P < 0. 11). In the treatment group, 54 patients with liver cirrhosis were followed up for an average of 5.2 years (1.1 ~ 11.6 years). In the control group, 53 patients with liver cirrhosis were followed up for an average of 3.4 years (1.0 ~ 16.4 years), 16 patients developed liver cancer and 3 patients died of hepatitis B. The cumulative incidence of liver cancer in the treatment group and the control group for 3 years and 5 years were 4.2 vs 28.30.73% (P0. 000), respectively. The cumulative mortality of the two groups for 3 years and 5 years was 0.6vsl7.3%, respectively. COX regression analysis showed that the baseline age was an independent risk factor for cirrhosis. Baseline cirrhosis is an independent risk factor for HCC. Conclusion: drug resistance and relapse will inevitably occur in some people after long-term lamivudine treatment, but as long as the standard LAM therapy is combined with comprehensive management, the virus replication can be restrained as much as possible for a long time. To maintain long-term stable liver function, reduce the incidence of liver cirrhosis, liver cancer and HBV related mortality. The age of treatment baseline is an independent risk factor for liver cirrhosis, while the baseline diagnosis of cirrhosis is an independent risk factor 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】：2014
【分類號】：R512.62
本文編號：2342377
[Abstract]:Objective: to investigate the clinical outcome of long-term lamivudine therapy and whole-course management in patients with chronic hepatitis B. Methods: this study was a retrospective-prospective cohort study. Non-randomized groups were divided into two groups: 1) treatment group: to establish LAM antiviral therapy cohort of chronic hepatitis B (CHB) and liver cirrhosis (LC). Through regular follow-up, monitoring related indicators, early detection of drug resistance, recurrence, timely adjustment of treatment plan, maximum inhibition of HBV DNA, stable liver function. 2) Historical control group: screening positive HBsAg from outpatients and inpatients since 1990. 576 patients with abnormal ALT or AST, HBV-DNA positive or HBeAg positive, were followed up for one year without antiviral therapy. The general data (sex, age, baseline E antigen) of the treatment group (sex, age, baseline E antigen) were matched with the treatment group according to 1:1 by the tendency score method (Propensity score method). Baseline diagnosis) 265 cases were used as historical control group. Survival analysis was used to calculate the cumulative incidence and annual incidence of clinical endpoint events (cirrhosis, liver cancer, death) from the cohort to the date of the last visit. The COX risk model was used to analyze the effects of the two groups on liver cirrhosis in patients with CHB/LC. Risk factors for liver cancer. Results: (1) in the treatment group, 265 cases of CHB (79.6%) and LC were treated with LAM, of which 238 cases (89.8%) were newly treated, male accounted for 74.3%, and the baseline E antigen positive was 57.7%. The average age was 35.7 鹵12 years. (2) in the historical control group, there were 265 cases of, CHB (80%, 74.3% male, the baseline E antigen positive was 59.2 years old, the average age was 35.7 鹵12 years old. To the last visit, the proportion of HBV DNA1000copy/ml in the treatment group and the control group was 89.1vs32.1; (3) in the treatment group, 87 cases (32.8%) had virological breakthrough, 85 of them were lamivudine resistant, and 1 was 3, the ratio of ALT < 1.3 times normal lower limit (ULN) was 89.8vs18.5. (3) in the treatment group, 87 cases (32.8%) had a virological breakthrough, among which 85 cases were lamivudine resistant. The cumulative drug resistance rate in 5 years was 6.1% and 38.9%, and the average annual drug resistance rate was 10.1%. The other 2 cases were resistant to lamivudine and adefovir ester. One hundred and nineteen cases (44.9%) stopped drug withdrawal and 72 cases (60.5%) recurred after withdrawal. Among them, 53.4% (39 / 73) of the patients reached the standard of stopping drug withdrawal < 2010 Chinese guidelines for the prevention and treatment of chronic hepatitis B. The recurrence rate after discontinuation of drugs was 73.3% (33 / 45). (_ 4) in the treatment group. The mean follow-up of 211 patients with chronic hepatitis B was 62 鹵32 months. 8 cases had cirrhosis, 3 cases had liver cancer and no death. In the control group, 212 patients with chronic hepatitis B were followed up for an average of 50 鹵31 months, 83 patients developed cirrhosis, 9 patients developed liver cancer and 3 patients died. The cumulative incidence of liver cirrhosis in the treatment group and the control group for 3 years and 5 years was 0.6 vs 13.8and 1.5 vs 20.8% (P < 0.000). The cumulative incidence of liver cancer in 3 years and 5 years was 0. 0 vs 2. 6% and 0. 9% vs 2. 6% (P < 0. 11). In the treatment group, 54 patients with liver cirrhosis were followed up for an average of 5.2 years (1.1 ~ 11.6 years). In the control group, 53 patients with liver cirrhosis were followed up for an average of 3.4 years (1.0 ~ 16.4 years), 16 patients developed liver cancer and 3 patients died of hepatitis B. The cumulative incidence of liver cancer in the treatment group and the control group for 3 years and 5 years were 4.2 vs 28.30.73% (P0. 000), respectively. The cumulative mortality of the two groups for 3 years and 5 years was 0.6vsl7.3%, respectively. COX regression analysis showed that the baseline age was an independent risk factor for cirrhosis. Baseline cirrhosis is an independent risk factor for HCC. Conclusion: drug resistance and relapse will inevitably occur in some people after long-term lamivudine treatment, but as long as the standard LAM therapy is combined with comprehensive management, the virus replication can be restrained as much as possible for a long time. To maintain long-term stable liver function, reduce the incidence of liver cirrhosis, liver cancer and HBV related mortality. The age of treatment baseline is an independent risk factor for liver cirrhosis, while the baseline diagnosis of cirrhosis is an independent risk factor 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】：2014
【分類號】：R512.62
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 羅生強(qiáng),張玲霞,張文謹(jǐn),蔡少平,高峰;拉米夫定治療慢性乙型肝炎停藥后肝炎復(fù)發(fā)的臨床觀察[J];實(shí)用肝臟病雜志;2004年04期
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