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.
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：