替诺福韦地索普西富马酸盐可减轻慢性乙型肝炎肝硬化患者

StephenW

Aliment Pharmacol Ther. 2019 Sep 16. doi: 10.1111/apt.15499. [Epub ahead of print]
Tenofovir disoproxil fumarate reduces hepatocellular carcinoma, decompensation and death in chronic hepatitis B patients with cirrhosis.
Liu K1,2, Choi J3, Le A4, Yip TC5,6, Wong VW5,6, Chan SL5,7, Chan HL5,6, Nguyen MH4, Lim YS3, Wong GL5,6.
Author information

1
    AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
2
    Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
3
    Department of Gastroenterology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.
4
    Division of Gastroenterology and Hepatology, Stanford University Medical Centre, Stanford, CA, USA.
5
    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
6
    Institute of Digestive Disease and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
7
    Department of Clinical Oncology and State Key Laboratory of Translation Oncology, Sir YK Pao Centre for Cancer, Hong Kong, Hong Kong.

Abstract
BACKGROUND:

Lamivudine and entecavir reduce hepatic events and death in chronic hepatitis B (CHB) patients with cirrhosis, but the impact of tenofovir disoproxil fumarate (TDF) is less well studied.
AIM:

To investigate the effectiveness of TDF therapy in CHB patients with cirrhosis.
METHODS:

We studied TDF-treated and untreated CHB patients with cirrhosis from three tertiary centres. TDF cohort included consecutive patients who received TDF for ≥12 months while the untreated cohort were historical controls receiving routine clinical care prior to the availability of anti-viral therapy. The primary outcome was 5-year cumulative probability of hepatocellular carcinoma (HCC) with secondary outcomes being hepatic decompensation and death or liver transplantation (LT).
RESULTS:

A total of 1088 (291 untreated and 797 TDF-treated) patients were included in the study. Five-year cumulative probabilities in untreated vs TDF-treated cohorts were 14.9% vs 9.8% for HCC (P = .07), 22.3% vs 5.9% for decompensation (P < .01) and 13.1% vs 1.1% for death or LT (P < .01) respectively. On multivariable Cox regression, TDF treatment was independently associated with reduced risks of HCC (adjusted hazard ratio [aHR] 0.46, P < .01), decompensating events (aHR 0.28, P = .01) and death or LT (aHR 0.06, P < .01). On sensitivity analyses, these risk reductions with TDF treatment were consistently demonstrated regardless of severity of liver disease and prior anti-viral treatment. TDF treatment led to sustained improvements in most validated prognostic scores for predicting HCC, decompensation and death.
CONCLUSIONS:

Compared to untreated patients, TDF treatment reduces the risks of HCC, hepatic decompensation and death in CHB patients with cirrhosis at 5 years.

© 2019 John Wiley & Sons Ltd.

PMID:
    31524304
DOI:
    10.1111/apt.15499

StephenW

Aliment Pharmacol Ther。 2019年9月16日doi：10.1111 / apt.15499。 [印刷前的电子版]
替诺福韦地索普西富马酸盐可减轻慢性乙型肝炎肝硬化患者的肝细胞癌，失代偿和死亡。
Liu K1,2，Choi J3，Le A4，Yip TC5,6，Wong VW5,6，Chan SL5,7，Chan HL5,6，Nguyen MH4，Lim YS3，Wong GL5,6。
作者信息

1
AW Morrow胃肠病学和肝脏中心，澳大利亚新南威尔士州悉尼皇家阿尔弗雷德王子医院。
2
澳大利亚新南威尔士州悉尼悉尼大学悉尼医学院。
3
韩国首尔蔚山大学医学院牙山医学系消化内科
4
斯坦福大学医学中心，美国加利福尼亚州斯坦福大学消化内科和肝病学系。
五
香港中文大学医学与治疗学系，香港，香港。
6
香港中文大学消化病研究所和消化疾病国家重点实验室，香港，香港。
7
香港香港YK Pao癌症中心临床肿瘤学系和翻译肿瘤学国家重点实验室。

抽象
背景：

拉米夫定和恩替卡韦可减轻慢性乙型肝炎（CHB）肝硬化患者的肝脏事件和死亡，但替诺福韦地索普西富马酸盐（TDF）的影响研究较少。
目标：

调查TDF治疗对CHB肝硬化患者的疗效。
方法：

我们从三个三级中心研究了TDF治疗和未治疗的肝硬化CHB患者。 TDF队列包括接受TDF≥12个月的连续患者，而未治疗的队列是在抗病毒治疗可用之前接受常规临床治疗的历史对照。主要结果是肝细胞癌（HCC）的5年增长概率，其次要结果是肝功能失代偿和死亡或肝移植（LT）。
结果：

该研究共纳入1088名患者（291名未治疗患者和797名TDF治疗患者）。未治疗组和TDF治疗组的五年累积概率分别为14.9％和9.8％（P = .07），22.3％对比失代偿为5.9％（P <.01）和13.1％对比死亡或LT为1.1％ （P <.01）。在多变量Cox回归分析中，TDF治疗与HCC风险降低（校正风险比[aHR] 0.46，P <.01），失代偿事件（aHR 0.28，P = .01）和死亡或LT（aHR 0.06，P）独立相关。 <.01）。在敏感性分析中，TDF治疗的这些风险降低始终如一，无论肝病的严重程度和先前的抗病毒治疗如何。 TDF治疗导致大多数经过验证的预后评分持续改善，用于预测HCC，失代偿和死亡。
结论：

与未治疗的患者相比，TDF治疗可降低5年肝硬化CHB患者发生HCC，肝功能失代偿和死亡的风险。

©2019 John Wiley＆Sons Ltd.

结论：
31524304
DOI：
10.1111 / apt.15499