抗病毒治疗期间较早的丙氨酸氨基转移酶正常化与慢性乙型

StephenW

Am J Gastroenterol. 2020 Jan 2. doi: 10.14309/ajg.0000000000000490. [Epub ahead of print]
Earlier Alanine Aminotransferase Normalization During Antiviral Treatment Is Independently Associated With Lower Risk of Hepatocellular Carcinoma in Chronic Hepatitis B.
Choi J1, Kim GA2, Han S3, Lim YS1.
Author information

1
    Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
2
    Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
3
    Department of Applied Statistics, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea.

Abstract
OBJECTIVES:

It was suggested that normalization of serum alanine aminotransferase (ALT) levels at 1 year of antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B (CHB). However, it remains unclear whether earlier ALT normalization is associated with lower hepatocellular carcinoma (HCC) risk, independent of fatty liver or cirrhosis and on-treatment virological response (VR), in patients with CHB.
METHODS:

We analyzed 4,639 patients with CHB who initiated treatment with entecavir or tenofovir using landmark analysis and time-dependent Cox analysis. We defined normal ALT as ≤35 U/L (men) and ≤25 U/L (women) and VR as serum hepatitis B virus DNA <15 IU/mL.
RESULTS:

During a median 5.6 years of treatment, 509 (11.0%) patients developed HCC. ALT normalization occurred in 65.6% at 1 year and 81.9% at 2 years and was associated with a significantly lower HCC risk in landmark (P < 0.001) and time-dependent Cox analyses (adjusted hazard ratio [AHR] 0.57; P < 0.001). Compared with ALT normalization within 6 months, delayed ALT normalization at 6-12, 12-24, and >24 months was associated with incrementally increasing HCC risk (AHR 1.40, 1.74, and 2.45, respectively; P < 0.001), regardless of fatty liver or cirrhosis at baseline and VR during treatment. By contrast, neither earlier VR (AHR 0.93; P = 0.53) nor earlier hepatitis B e antigen seroclearance (AHR 0.91; P = 0.31) was associated with a significantly lower HCC risk.
DISCUSSION:

In patients with CHB treated with entecavir or tenofovir, earlier ALT normalization was independently associated with proportionally lower HCC risk, regardless of fatty liver or cirrhosis at baseline and on-treatment VR.

PMID:
    31895708
DOI:
    10.14309/ajg.0000000000000490

StephenW

我是J胃肠。 2020年1月2日。doi：10.14309 / ajg.0000000000000490。 [Epub提前发布]
抗病毒治疗期间较早的丙氨酸氨基转移酶正常化与慢性乙型肝炎肝细胞癌的低风险独立相关。
崔J1，金GA2，韩S3，林YS1。
作者信息

1个
    韩国首尔蔚山大学医学院附属牙山医学中心肝病消化内科。
2
    韩国首尔庆熙大学医学院内科系。
3
    韩国京畿道城南市，加川大学应用统计系。

抽象
目标：

有人提出，抗病毒治疗1年时血清丙氨酸转氨酶（ALT）水平正常与慢性乙型肝炎（CHB）患者发生肝事件的风险较低有关。然而，尚不清楚早期的ALT正常化是否与较低的肝细胞癌（HCC）风险相关，该风险独立于脂肪肝或肝硬化以及治疗中的病毒学应答（VR），在CHB患者中。
方法：

我们使用地标分析和时间依赖性Cox分析法分析了4,639例开始使用恩替卡韦或替诺福韦治疗的CHB患者。我们将正常ALT定义为≤35U / L（男性）和≤25U / L（女性），将VR定义为血清乙型肝炎病毒DNA <15 IU / mL。
结果：

在中位治疗5.6年中，有509名（11.0％）患者发展为HCC。 ALT正常化在1年时发生率为65.6％，在2年时发生时为81.9％，并且与标志性（P <0.001）和时间依赖性Cox分析中的HCC风险显着降低有关（校正后的危险比[AHR] 0.57； P <0.001） 。与6个月内的ALT正常化相比，在6-12、12-24和> 24个月的ALT正常化延迟与HCC风险的增加相关（分别为AHR 1.40、1.74和2.45； P <0.001），而不论脂肪在基线和治疗期间VR肝或肝硬化。相比之下，早期的VR（AHR 0.93; P = 0.53）或早期的B型肝炎e抗原血清清除（AHR 0.91; P = 0.31）均与HCC风险明显降低无关。
讨论：

在使用恩替卡韦或替诺福韦治疗的CHB患者中，较早的ALT正常化与比例降低的HCC风险独立相关，无论基线时和治疗中VR的脂肪肝或肝硬化如何。

PMID：
    31895708
DOI：
    10.14309 / ajg.0000000000000490