核苷（酸）类似物的补偿乙肝肝硬化患者无或小的食管静脉

StephenW

Research Article
The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study

• Pietro Lampertico1,
• Federica Invernizzi1,
• Mauro Viganò2,
• Alessandro Loglio1,
• Giampaolo Mangia1,
• Floriana Facchetti1,
• Massimo Primignani1,
• Manol Jovani1,
• Massimo Iavarone1,
• Mirella Fraquelli3,
• Giovanni Casazza4,
• Roberto de Franchis5,
• Massimo Colombo1, ,
  

• 1 “A.M. and A. Migliavacca” Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
• 2 Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Italy
• 3 Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
• 4 Department of Biomedical and Clinical Sciences, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy
• 5 Division of Gastroenterology, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy
  

Received 22 October 2014, Revised 14 May 2015, Accepted 8 June 2015, Available online 19 June 2015
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Background & Aims

Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known.

Methods

A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months.

Results

Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52–92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5–20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24–42%) and 76% (95% CI: 67–83%), respectively.

Conclusions

Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV.

Abbreviations

• EV, esophageal varices;
• NUC, nucleos(t)ide analogs;
• GI, gastrointestinal;
• LMV, lamivudine;
• LMV-R, lamivudine resistance;
• HCC, hepatocellular carcinoma;
• HBV, hepatitis B virus;
• HVPG, hepatic venous pressure gradient;
• EGDS, esophago-gastroduodenoscopy;
• PHG, portal hypertensive gastropathy;
• GOV, gastro-esophageal varices;
• IGV, isolated gastric varices;
• LT, liver transplantation;
• RWM, red wale marks;
• HIV, human immunodeficiency virus;
• US, abdominal ultrasound
  

Keywords

• Hepatitis B virus;
• Cirrhosis;
• Esophageal varices;
• Nucleos(t)ide analogs;
• Gastrointestinal bleeding;
• Hepatocellular carcinoma;
• HBsAg clearance;
• Transient elastography
  

Corresponding author. Address: Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università di Milano, Via F. Sforza 35, 20122 Milan, Italy. Tel.: +39 0255035432; fax: +39 0250320700.

Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier Ireland Ltd. All rights reserved.

StephenW

研究论文
的核苷（酸）类似物的补偿乙肝肝硬化患者无或小的食管静脉曲张的长期效益：12年的前瞻性队列研究

    彼得Lampertico1，费德里卡Invernizzi1，毛罗Viganò2，亚历山德罗Loglio1，詹保罗Mangia1，弗洛里亚纳Facchetti1，马西莫Primignani1，Manol Jovani1，马西莫Iavarone1，米雷拉Fraquelli3，乔瓦尼Casazza4，罗伯托·德Franchis5，马西莫Colombo1，

    1“上午和A. Migliavacca“中心肝病，胃肠病学和肝病基金会IRCCS钙'格兰达Ospedale马焦雷位于Policlinico如Università德利阿布鲁Studi住宅米兰，米兰，意大利分部
    2科肝病的，Ospedale圣朱塞佩如Università德利阿布鲁Studi住宅米兰，意大利
    胃肠病学和内窥镜检查，基金会IRCCS钙'格兰达Ospedale马焦雷位于Policlinico如Università德利阿布鲁Studi住宅米兰，米兰，意大利的3部
    生物医学和临床科学，Ospedale路易吉·萨科如Università德利阿布鲁Studi住宅米兰，米兰，意大利4部
    5司消化，Ospedale路易吉·萨科如Università德利阿布鲁Studi住宅米兰，米兰，意大利

    收到的2014年22月，修订2015年5月14日，接受8 2015年6月，可在线19 2015年6月

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        DOI：10.1016 / j.jhep.2015.06.006
    获得权利和内容

背景和目的

食管静脉曲张（EV）是在代偿性肝硬化疾病严重程度的标志物由于乙型肝炎病毒（HBV），这也预测肝细胞癌（HCC）的危险，临床失代偿和预期的肝相关死亡。动力和电动汽车的下长期抑制乙肝患者经核苷（酸）类似物（NUC）预后意义，鲜为人知。
方法

标准化协议（巴韦诺），包括414上消化道（GI）内镜应用于107 HBeAg阴性的补偿肝硬化患者（93％Child-Pugh分级A）为12（2〜17岁）NUC治疗的平均期间。患者最初开始拉米夫定（LMV），然后产生耐药性（LMV-R）是谁，被阿德福韦早期用药获救，或者被转换为替诺福韦。监测包括血清HBV DNA每三个月和腹部超声检查每半年一次。
结果

27例患者的基线F1 EV这倒退18，在八个保持不变，进步的一个病人; EV回归的12年累积发生率为83％（95％CI：52-92％）。从头F1 / F2电动汽车开发的6/80患者有10％（95％CI：5-20％），12年的累计发生率。六七例从头静脉曲张或预先存在的静脉曲张的发展有两种临床突破，由于LMV-R和/或开发出肝癌。从EV破裂出血没有发生，死亡12例（9 HCC）和15例移植（13 HCC）：HCC和总生存期的12年累积发生率为33％（95％CI：24-42％）和76％ （95％CI：67-83％），分别。
结论

乙肝病毒e抗原阴性的患者代偿性肝硬化长期药理抑制导致预先存在的EV伴随显影从头EV的风险可忽略一个显著消退。
缩写

    EV，食管静脉曲张; NUC，核苷（酸）类似物;胃肠道，胃肠道; LMV，拉米夫定; LMV-R，拉米夫定耐药;肝癌，肝细胞癌;乙肝病毒，B型肝炎病毒; HVPG，肝静脉压力梯度; EGDS，食管胃十二指肠镜检查; PHG，门脉高压性胃病; GOV，胃 - 食管静脉曲张; IGV，孤立性胃静脉曲张; LT，肝移植; RWM，红色征标记;艾滋病毒，人类免疫缺陷病毒;美国，腹部超声

关键词

    乙型肝炎病毒;肝硬化;食管静脉曲张;核苷（酸）类似物;胃肠道出血;肝癌; HBsAg清除;瞬时弹性成像

    通讯作者。地址：胃肠病学和肝病基金会IRCCS钙'格兰达Ospedale马焦雷位于Policlinico，UNIVERSITA米兰的Via F.斯福尔扎35，20122米​​兰，意大利的分部。电话：+39 0255035432;传真：+39 0250320700。

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