CAJ | 학술논문

　　背景：长期应用拉米夫定导致YMDD变异是肝移植后乙肝复发的主要原因。近年来恩替卡韦等新型强效低耐药抗病毒药物在乙肝相关性肝病中取得的很好的疗效，但对其在肝移植后预防乙肝复发作用的研究较为少见。目的：分析恩替卡韦联合小剂量乙型肝炎人免疫球蛋白在肝移植后预防乙型肝炎复发的作用。方法：回顾性分析253例乙型肝炎病毒相关性肝移植患者的随访资料。所有患者肝移植前即开始给予核苷(酸)类似物预防，肝移植中和移植后均给予核苷(酸)类似物联合低剂量乙型肝炎人免疫球蛋白的预防方案。在所有患者和具有乙肝复发危险因素(术前HBeAg阳性、乙型肝炎病毒DNA阳性、肝癌、YMDD变异)的患者中分别比较恩替卡韦+乙型肝炎人免疫球蛋白和拉米夫定+乙型肝炎人免疫球蛋白预防的不同效果。结果与结论：共完成253例乙型肝炎病毒相关性肝移植，死亡29例。拉米夫定组共202例，有16例复发，26例死亡，复发率为7.92%(16/202)；恩替卡韦组共51例，未发现乙型肝炎病毒复发，3例死亡，两组患者复发率、死亡率差异不明显。恩替卡韦+乙型肝炎人免疫球蛋白与拉米夫定+乙型肝炎人免疫球蛋白相比，能有效降低具有乙肝复发危险因素患者的乙肝复发率。复发后均停用乙型肝炎人免疫球蛋白，并调整核苷(酸)类似物，经治疗乙型肝炎病毒DNA均<500 IU/mL，肝功能稳定。Log-rank检验显示乙型肝炎病毒复发后及时治疗对患者长期存活率无明显影响。结果说明，在核苷(酸)类似物联合乙型肝炎人免疫球蛋白预防方案的预防下，乙肝复发后及时处理对预后影响不大。恩替卡韦联合乙型肝炎人免疫球蛋白能有效预防乙肝复发。对于具有危险因素的患者，恩替卡韦联合乙型肝炎人免疫球蛋白较拉米夫定联合乙型肝炎人免疫球蛋白可以更有效地降低肝移植后乙肝复发率。　　揹景：長期應用拉米伕定導緻YMDD變異是肝移植後乙肝複髮的主要原因。近年來恩替卡韋等新型彊效低耐藥抗病毒藥物在乙肝相關性肝病中取得的很好的療效，但對其在肝移植後預防乙肝複髮作用的研究較為少見。目的：分析恩替卡韋聯閤小劑量乙型肝炎人免疫毬蛋白在肝移植後預防乙型肝炎複髮的作用。方法：迴顧性分析253例乙型肝炎病毒相關性肝移植患者的隨訪資料。所有患者肝移植前即開始給予覈苷(痠)類似物預防，肝移植中和移植後均給予覈苷(痠)類似物聯閤低劑量乙型肝炎人免疫毬蛋白的預防方案。在所有患者和具有乙肝複髮危險因素(術前HBeAg暘性、乙型肝炎病毒DNA暘性、肝癌、YMDD變異)的患者中分彆比較恩替卡韋+乙型肝炎人免疫毬蛋白和拉米伕定+乙型肝炎人免疫毬蛋白預防的不同效果。結果與結論：共完成253例乙型肝炎病毒相關性肝移植，死亡29例。拉米伕定組共202例，有16例複髮，26例死亡，複髮率為7.92%(16/202)；恩替卡韋組共51例，未髮現乙型肝炎病毒複髮，3例死亡，兩組患者複髮率、死亡率差異不明顯。恩替卡韋+乙型肝炎人免疫毬蛋白與拉米伕定+乙型肝炎人免疫毬蛋白相比，能有效降低具有乙肝複髮危險因素患者的乙肝複髮率。複髮後均停用乙型肝炎人免疫毬蛋白，併調整覈苷(痠)類似物，經治療乙型肝炎病毒DNA均<500 IU/mL，肝功能穩定。Log-rank檢驗顯示乙型肝炎病毒複髮後及時治療對患者長期存活率無明顯影響。結果說明，在覈苷(痠)類似物聯閤乙型肝炎人免疫毬蛋白預防方案的預防下，乙肝複髮後及時處理對預後影響不大。恩替卡韋聯閤乙型肝炎人免疫毬蛋白能有效預防乙肝複髮。對于具有危險因素的患者，恩替卡韋聯閤乙型肝炎人免疫毬蛋白較拉米伕定聯閤乙型肝炎人免疫毬蛋白可以更有效地降低肝移植後乙肝複髮率。
　　배경：장기응용랍미부정도치YMDD변이시간이식후을간복발적주요원인。근년래은체잡위등신형강효저내약항병독약물재을간상관성간병중취득적흔호적료효，단대기재간이식후예방을간복발작용적연구교위소견。목적：분석은체잡위연합소제량을형간염인면역구단백재간이식후예방을형간염복발적작용。방법：회고성분석253례을형간염병독상관성간이식환자적수방자료。소유환자간이식전즉개시급여핵감(산)유사물예방，간이식중화이식후균급여핵감(산)유사물연합저제량을형간염인면역구단백적예방방안。재소유환자화구유을간복발위험인소(술전HBeAg양성、을형간염병독DNA양성、간암、YMDD변이)적환자중분별비교은체잡위+을형간염인면역구단백화랍미부정+을형간염인면역구단백예방적불동효과。결과여결론：공완성253례을형간염병독상관성간이식，사망29례。랍미부정조공202례，유16례복발，26례사망，복발솔위7.92%(16/202)；은체잡위조공51례，미발현을형간염병독복발，3례사망，량조환자복발솔、사망솔차이불명현。은체잡위+을형간염인면역구단백여랍미부정+을형간염인면역구단백상비，능유효강저구유을간복발위험인소환자적을간복발솔。복발후균정용을형간염인면역구단백，병조정핵감(산)유사물，경치료을형간염병독DNA균<500 IU/mL，간공능은정。Log-rank검험현시을형간염병독복발후급시치료대환자장기존활솔무명현영향。결과설명，재핵감(산)유사물연합을형간염인면역구단백예방방안적예방하，을간복발후급시처리대예후영향불대。은체잡위연합을형간염인면역구단백능유효예방을간복발。대우구유위험인소적환자，은체잡위연합을형간염인면역구단백교랍미부정연합을형간염인면역구단백가이경유효지강저간이식후을간복발솔。
BACKGROUND:Prolonged therapy with lamivudine has been associated with tyrosine-methionine-aspartate-aspartate mutation, which results in hepatitis B recurrence. Recently, antiviral agents, such as entecavir, have high efficacy and low resistance rate in hepatitis B-related liver disease. However, the researches on the effect of entecavir in preventing hepatitis B recurrence after liver transplantation are rare. OBJECTIVE:To investigate the effect of entecavir combined with low-dose hepatitis B immunoglobulin in preventing hepatitis B recurrence after liver transplantation. METHODS:The fol ow-up data of 253 patients who had liver transplantation for hepatitis B virus related liver disease were retrospectively analyzed. Al patients received nucleoside analogues therapy formal y before liver transplantation. The effects of entecavir+hepatitis B immunoglobulin and lamivudine+hepatitis B immunoglobulin were compared in al the patients and the patents with hepatitis B recurrence risk factors (positive preoperative HBeAg, DNA-positive hepatitis B virus, hepatoma and tyrosine-methionine-aspartate-aspartate mutation). RESULTS AND CONCLUSION:A total of 253 patients received hepatitis B virus-related liver transplantation, and 29 patients died. There were 202 patients in lamivudine group in which 26 patients were dead and 16 patients had hepatitis B virus recurrence, and the recurrence rate was 7.92%(16/202). However, entecavir group had 51 patients without hepatitis B virus recurrence in which three patients were dead. There were significant differences in the mortality rate and recurrence rate between two groups. Compared with the lamivudine+hepatitis B immunoglobulin, entecavir+hepatitis B immunoglobulin could effectively reduce the recurrence rate of the patients with hepatitis B virus-related risk factors. Hepatitis B immunoglobulin was terminated and nucleoside analogues were modulated when recurrence appeared. Al patients hepatitis B virus DNA were control ed less than 500 IU/mL and liver function returned to normal level. Log-rank test showed that there was no significant difference in the long-term survival rate after timely treatment of hepatitis B virus recurrence. With the prevention of nucleoside analogues combined with hepatitis B immunoglobulin therapy, timely treatment of hepatitis B recurrence has little influence on the prognosis. Entecavir combined with hepatitis B immunoglobulin can effectively prevent the hepatitis B recurrence. For the patients with hepatitis B virus-related risk factors, entecavir combined with hepatitis B immunoglobulin can better reduce the recurrence rate of hepatitis B than lamivudine+hepatitis B immunoglobulin after liver transplantation.