长期慢性HBV治疗结果与一般人群相似

StephenW

Long-term chronic HBV treatment outcomes similar to general population

Papatheodoridis GV, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2018.01.031.
February 9, 2018

Patients treated with long-term combined entecavir and tenofovir for chronic hepatitis B had overall and liver-related 8-year survival rates similar to the general population, except for those with hepatocellular carcinoma, according to recently published data.

“The use of current first-line nucleos(t)ide analogues (NAs), such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF), has offered prolonged inhibition of HBV replication in almost all compliant [chronic HBV (CHB)] patients, improvement of liver necroinflammation and fibrosis, sometimes reversion of histological cirrhosis and prevention or even reversal of early liver decompensation,” George V. Papatheodoridis, MD, PhD, from the Laiko General Hospital, Greece, and colleagues wrote.


To evaluate the survival outcomes and effects of long-term treatment with ETV and TDF, Papatheodoridis and colleagues enrolled 1,951 adult, Caucasian patients with CHB, 526 of whom had compensated cirrhosis.

During a median follow-up of 6 years (range, 1-14 years), 84 patients died of any cause. The 8-year overall cumulative probabilities were 99.7% at 1 year, 97.8% at 3 years, 95.9% at 5 years and 94.1% at 8 years.

Multivariate analysis showed that older age per year (HR = 1.04; 95% CI, 1.02-1.06), HCC development (HR = 35.95; 95% CI, 21.14-61.11) and lower platelet levels per 104/mm3 (HR = 0.96; 95% CI, 0.91-1) correlated independently with higher risk for mortality.

Thirty-four patients died of liver disease. The overall cumulative probabilities were 99.9% at 1 year, 99.4% at 3 years, 98.3% at 5 years and 97.4% at 8 years. Multivariate analysis showed that development of HCC correlated independently with a higher risk for liver-related mortality (HR = 139.2; 95% CI, 48.59-398.79).

One hundred-eighteen patients developed HCC. After a median of 19.2 months of follow-up, three patients with HCC died due to causes unrelated to liver disease, 29 died due to HCC and 15 underwent liver transplantation. The overall mortality rate was 5.88 (95% CI, 3.85-7.7) deaths per 100 patients with HCC per year.

The researchers matched the study cohort by age, sex, country and calendar year with the general population to compare mortality rates. The overall standardized mortality ratio (SMR) was 0.82 (95% CI, 0.66-1.03), 0.78 for men (95% CI, 0.63-1.59) and 1 for women (95% CI, 0.41-0.82).

Compared with the general population, the SMR was lower in patients without cirrhosis (0.58; 95% CI, 0.41-0.82), similar in patients with cirrhosis (1.22; 95% CI, 0.9-1.66), lower in patients who did not develop HCC regardless of baseline cirrhosis (0.58; 95% CI, 0.44-0.77), and higher in patients who developed HCC (3.09; 95% CI, 2.13-4.48).

“Given that the existing CHB patients, particularly those who remain undiagnosed are becoming older and perhaps are progressing to more advanced stages of liver disease, the incidence and mortality of HBV related HCC are expected to increase in the near future,” the researchers wrote. “Thus, effective screening programs should be implemented in order to diagnose and treat the existing CHB patients at younger ages and earlier stages. Since HCC may also develop in effectively treated patients, careful evaluation of the patients’ HCC risk and HCC surveillance are mandatory.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

StephenW

长期慢性HBV治疗结果与一般人群相似

Papatheodoridis GV等人J Hepatol。 2017; DOI：10.1016 / j.jhep.2018.01.031。
2018年2月9日

据最近公布的数据显示，长期联合恩替卡韦和替诺福韦治疗慢性乙型肝炎的患者的总体和肝脏相关8年生存率与一般人群相似，但肝细胞癌患者除外。

“恩替卡韦（ETV）和富马酸替诺福韦酯（TDF）等目前一线核苷酸类似物（NAs）的使用在几乎所有顺应性[慢性HBV（CHB）]患者，改善肝脏坏死性炎症和纤维化，有时可以恢复组织学的肝硬化，预防甚至逆转早期肝功能失代偿，“希腊Laiko综合医院的George V. Papatheodoris博士及其同事写道。


为了评估ETV和TDF长期治疗的生存结果和疗效，Papatheodoridis及其同事招募了1,951名成人，CHB高加索患者，其中526名患有代偿性肝硬化。

在中位随访6年（范围1-14年）期间，84例患者死于任何原因。 8年总累计概率在1年时为99.7％，3年时为97.8％，5年时为95.9％，8年时为94.1％。

多变量分析显示，每年年龄较大（HR = 1.04; 95％CI，1.02-1.06），HCC发展（HR = 35.95; 95％CI，21.14-61.11）和每104 / mm3血小板水平降低（HR = 0.96; 95％CI，0.91-1）独立相关，死亡风险较高。

34名患者死于肝病。 1年累计概率为99.9％，3年为99.4％，5年为98.3％，8年为97.4％。多因素分析显示HCC的发生与肝脏相关死亡风险相关（HR = 139.2; 95％CI，48.59-398.79）。

有110名患者发展为HCC。中位随访19.2个月后，3例HCC患者因与肝病无关的原因死亡，29例因HCC死亡，15例接受肝移植。每100例HCC患者每年死亡总数为5.88（95％CI，3.85-7.7）。

研究人员将年龄，性别，国家和日历年的研究队列与普通人群进行比较，以比较死亡率。总体标准化死亡率（SMR）为0.82（95％CI，0.66-1.03），男性为0.78（95％CI，0.63-1.59），女性为1（95％CI，0.41-0.82）。

与一般人群相比，无肝硬化患者的SMR较低（0.58; 95％CI，0.41-0.82），肝硬化患者相似（1.22; 95％CI，0.9-1.66），未发展的患者较低无论基线肝硬化（0.58; 95％CI，0.44-0.77），HCC发生HCC的患者（3.09; 95％CI，2.13-4.48）更高。

研究人员写道：“考虑到现有的慢性乙型肝炎患者，特别是那些尚未确诊的慢性乙型肝炎患者年龄越来越大，可能正在进展至更晚期的肝脏疾病，预计在不久的将来HBV相关HCC的发病率和死亡率会增加。 “因此，应该实施有效的筛查计划，以便诊断和治疗现有的CHB患者在年轻和早期阶段。由于HCC也可能在有效治疗的患者中发展，所以对患者的HCC风险和HCC监测进行仔细评估是强制性的。“ - Talitha Bennett

披露：作者报告没有相关的财务披露。

疯一点好

   
    题目是不是说抗病毒治疗结果与不治疗的结果是一样的。
    年龄是个敏感的话题啊，
   

StephenW

回复 疯一点好 的帖子

不是.

是说抗病毒治疗慢性乙型肝炎的患者的生存率与一般人群相似, 但肝细胞癌患者除外。

意思是: 乙型肝炎的患者治疗后, 如果有或发生HCC, 生存率与一般人群比较低.
因此应该诊断和治疗现有的CHB患者在年轻和早期阶段(发生HCC率低), 治疗后生存率与一般人群相似.

疯一点好

谢谢史蒂芬

StephenW

J Hepatol. 2018 Feb 7. pii: S0168-8278(18)30081-3. doi: 10.1016/j.jhep.2018.01.031. [Epub ahead of print]
8-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population.
Papatheodoridis GV1, Sypsa V2, Dalekos G3, Yurdaydin C4, Van Boemmel F5, Buti M6, Goulis J7, Luis Calleja J8, Chi H9, Manolakopoulos S10, Loglio A11, Siakavellas S12, Gatselis N3, Keskın O4, Lehretz M5, Savvidou S7, de la Revilla J8, Hansen BE9, Kourikou A10, Vlachogiannakos I12, Galanis K3, Idilman R4, Colombo M13, Esteban R6, Janssen HLA14, Berg T5, Lampertico P11.
Author information

1
    Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece;. Electronic address: [email protected].
2
    Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece.
3
    Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece.
4
    Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
5
    Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Germany.
6
    Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain.
7
    4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
8
    Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.
9
    Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.
10
    2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Athens, Greece.
11
    CRC "AM e A Migliavacca" Center for Liver Disease, Division of Gastrotnerology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
12
    Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
13
    Humanitas Clinical and Research Centre, Rozzano, Italy.
14
    Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.

Abstract
BACKGROUND/AIMS:

The effects of long-term antiviral therapy on survival have not been adequately assessed in chronic hepatitis B (CHB). In this 10-center, ongoing cohort study, we evaluated the probability of survival and factors affecting survival in Caucasian CHB patients treated with long-term entecavir/tenofovir therapy.
METHODS:

We included 1951 adult Caucasians with CHB with or without compensated cirrhosis and no hepatocellular carcinoma (HCC) at baseline who received entecavir/tenofovir for ≥12 months (median: 6 years). Kaplan-Meier estimates of cumulative survival over time were obtained. Standardized mortality ratios (SMR) were calculated by comparing death rates with the Human Mortality Databases.
RESULTS:

The 1-, 5- and 8-year cumulative probabilities were 99.7%, 95.9% and 94.1% for overall survival, 99.9%, 98.3% and 97.4% for liver related survival and 99.9%, 97.8% and 95.8% for transplantation free liver related survival. Overall mortality was independently associated with older age and HCC development, liver related mortality with HCC development only and transplantation free liver related mortality with HCC development and lower platelets at baseline. Baseline cirrhosis was not independently associated with any type of mortality. Compared to general population, mortality was not significantly different in all CHB patients (SMR: 0.82), while it was lower in patients without HCC regardless of baseline cirrhosis (SMR: 0.58) and higher in patients who developed HCC (SMR: 3.09).
CONCLUSION:

Caucasian patients with CHB and compensated liver disease treated with long-term entecavir/tenofovir therapy have excellent overall and liver related 8-year survival, which is similar to that of the general population. HCC is the main factor affecting their overall mortality and the only factor affecting their liver related mortality.
LAY SUMMARY:

Caucasian chronic hepatitis B patients with or without compensated cirrhosis treated with long-term entecavir or tenofovir therapy have an excellent overall 8-year survival which is similar to that of the general population. Hepatocellular carcinoma is the main factor affecting their overall mortality and the only factor affecting liver related mortality in this setting.

Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
KEYWORDS:

Antiviral therapy; Cirrhosis; Hepatitis B; Hepatocellular carcinoma; Liver transplantation

PMID:
    29427727
DOI:
    10.1016/j.jhep.2018.01.031

StephenW

J Hepatol。 2018年2月7日。pii：S0168-8278（18）30081-3。 Doi：10.1016 / j.jhep.2018.01.031。 [电子版提前打印]
长期使用恩替卡韦或替诺福韦治疗的慢性乙型肝炎患者的8年生存率与一般人群相似。
Papatheodoridis GV1 Sypsa V2 Dalekos G3 Yurdaydin C4 Van Boemmel F5 Buti M6 Goulis J7 Luis Calleja J8 Chi H9 Manolakopoulos S10 Loglio A11 Siakavellas S12 Gatselis N3KeskınO4 Lehretz M5 Savvidou S7， de Revilla J8，Hansen BE9，Kourikou A10，Vlachogiannakos I12，Galanis K3，Idilman R4，Colombo M13，Esteban R6，Janssen HLA14，Berg T5，Lampertico P11。
作者信息

1
希腊雅典莱科综合医院雅典卡波迪大学医学院胃肠病学系;电子地址：[email protected]。
2
卫生，流行病学和医学统计学系，希腊雅典国立医学院和卡波迪大教​​堂大学。
3
希腊拉里萨Thessalia大学医学院内科。
4
土耳其安卡拉安卡拉大学医学院消化内科。
五
德国莱比锡大学医院消化科和风湿科门诊部。
6
西班牙巴塞罗纳大学希瓦伦大学和Ciberehd大学医院。
7
希腊塞萨洛尼基塞萨洛尼基医学院亚里士多德大学第四内科医学系。
8
医院U Puerta de Hierro，IDIPHIM CIBeehd，马德里，西班牙。
9
荷兰鹿特丹大学医学中心Erasmus MC胃肠病学和肝病学系。
10
第二内科医学院，国立医科大学和希腊雅典Kapodistrian大学。
11
CRC“AM e A Migliavacca”肝病中心，胃病学和肝病学部，Fondazione IRCCSCàGranda Ospedale Maggiore Policlinico，米兰大学，意大利米兰大学。
12
希腊雅典莱科综合医院雅典卡波迪大学医学院胃肠病学系。
13
Humanitas临床和研究中心，罗扎诺，意大利。
14
荷兰鹿特丹大学医学中心Erasmus MC消化内科及肝病科;加拿大安大略省多伦多大学健康网络多伦多西部和综合医院肝脏诊所。

抽象
背景/目的：

慢性乙型肝炎（CHB）中长期抗病毒治疗对生存的影响尚未得到足够的重视。在这个10中心，正在进行的队列研究中，我们评估了长期使用恩替卡韦/替诺福韦治疗的高加索人CHB患者的生存概率和影响生存的因素。
方法：

我们纳入了1951例成人高加索人CHB伴或不伴肝硬化，且在接受恩替卡韦/替诺福韦≥12个月（中位数：6年）的基线时无肝细胞癌（HCC）。获得了随时间的累积存活的标准Kaplan-Meier估计。通过比较死亡率与人类死亡率数据库来计算标准化死亡率（SMR）。
结果：

1年，5年和8年的累积概率分别为99.7％，95.9％和94.1％的总生存率，99.9％，98.3％和97.4％的肝相关生存率和99.9％，97.8％和95.8％相关的生存。总体死亡率独立与年龄和HCC发病年龄独立相关，与HCC发生相关的肝脏相关死亡率以及与HCC发生和基线时血小板下降无关的移植肝相关死亡率。基线肝硬化不是与任何类型的死亡率独立相关。在一般人群中，所有CHB患者的死亡率无显着性差异（SMR：0.82），无肝硬化患者（SMR：0.58）的HCC患者死亡率较低（SMR：3.09）。
结论：

长期使用恩替卡韦/替诺福韦治疗的慢性乙型肝炎和代偿性肝病的白人患者具有优良的总体和肝脏相关的8年生存率，这与一般人群相似。 HCC是影响其总体死亡率的主要因素，也是影响其肝脏相关死亡率的唯一因素。
总结：

经长期恩替卡韦或替诺福韦治疗的有或无代偿性肝硬化的高加索慢性乙型肝炎患者的总体8年生存率与一般人群相似。肝细胞癌是影响其总体死亡率的主要因素，也是影响肝脏相关死亡率的唯一因素。

版权所有©2018年欧洲肝脏研究协会。由Elsevier B.V.出版。保留所有权利。
关键词：

抗病毒治疗;肝硬化;乙型肝炎;肝细胞癌;肝移植

结论：
29427727
DOI：
10.1016 / j.jhep.2018.01.031

newchinabok

JOH丨慢乙肝患者接受恩替卡韦或替诺福韦长期治疗的8年生存率与一般人群相似
发表时间：2018-02-11 标签： 新知 乙肝 相关搜索： CHB HCC 肝硬化 抗病毒治疗 肝移植

慢性乙型肝炎（CHB）尚缺乏长期抗病毒治疗对其生存期影响的充分评估数据。近日，来自希腊Laiko综合医院的Papatheodoridis等对接受长期恩替卡韦/替诺福韦治疗的高加索CHB患者的生存率和影响其生存的因素进行了分析。

研究发现：经长期恩替卡韦或替诺福韦治疗的有或无代偿性肝硬化的高加索CHB患者具有较好的总体和肝脏相关8年生存率，与一般人群相似；肝细胞癌（HCC）是影响其总体死亡率的主要因素，也是影响其肝脏相关死亡率的唯一因素。

研究者自10家中心纳入1951例高加索成人CHB患者。这些患者伴或不伴代偿性肝硬化，且基线时无HCC，接受恩替卡韦或替诺福韦治疗≥12个月（中位数：6年）。应用Kaplan-Meier评估随时间推移的累积生存变化。通过比较死亡率与人类死亡率数据库来计算标准化死亡率（SMR）。

结果，1年、5年和8年的累积生存分别为：总生存率99.7%、95.9%和94.1%，肝脏相关生存率99.9%、98.3%和97.4%，移植肝的相关生存率99.9%、97.8%和95.8%。总体死亡率与年龄较大和HCC发生独立相关，肝脏相关死亡率仅与HCC发生相关，移植肝的相关死亡率与HCC发生和基线时血小板较低有关。

基线肝硬化与任何类型的死亡率均无独立相关性。相比于一般人群，所有CHB患者的死亡率无显著差异（SMR：0.82），而无HCC（尽管基线合并肝硬化）患者的死亡率较低（SMR：0.58），进展至HCC的患者的死亡率较高（SMR：3.09）。