慢性乙型肝炎患者接受核苷酸/核苷类似物治疗后，丙氨酸转氨酶水平作为治疗靶点。
Alanine aminotransferase levels as therapeutic targets after nucleotide/nucleoside analog therapy in patient with chronic hepatitis B.
作者信息
Kirino Sakura, Tamaki Nobuharu, Kurosaki Masayuki, Kaneko Shun, Inada Kento, Tanaka Yuki, Ishido Shun, Yamashita Koji, Nobusawa Tsubasa, Matsumoto Hiroaki, Hayakawa Yuka, Kakegawa Tatsuya, Higuchi Mayu, Takaura Kenta, Tanaka Shohei, Maeyashiki Chiaki, Yasui Yutaka, Takahashi Yuka, Tsuchiya Kaoru, Nakanishi Hiroyuki, Okamoto Ryuichi, Izumi Namiki
机构信息
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
出版信息
Hepatol Res. 2023 Jan;53(1):35-42. doi: 10.1111/hepr.13839. Epub 2022 Oct 4.
AIM
Alanine aminotransferase (ALT) is a criterion for the introduction of nucleotide/nucleoside analog (NA), and ALT levels are decreased by NA treatment. However, the association between post-treatment ALT levels and hepatocellular carcinoma (HCC) risk remains unclear. To fill this gap, we aimed to establish a target value of ALT level during NA treatment.
METHODS
In total, 413 patients with chronic hepatitis B who received entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate were enrolled. The subsequent development of HCC was examined and a target value of ALT level during NA treatment as a risk marker for HCC was evaluated.
RESULTS
The median follow-up duration was 5.1 years, during which time 27 patients (8.6%) developed HCC. ALT level at the start of treatment was not associated with HCC development (p = 0.08). When stratified by ALT at 1 year after NA initiation, the cumulative 3- and 5-year rates of HCC for patients with ALT ≥21 IU/L were 11.5% and 18.1%, and those with ALT <21 IU/L was 2.3% and 6.5%, respectively. Patients with ALT <21 IU/L had a significantly lower risk of HCC development compared with patients with ALT ≥21 IU/L (p = 0.002). In multivariable analysis adjusting age, sex, and platelet counts, ALT ≥21 IU/L was an independent risk factor of HCC development with hazard ratio of 4.5 (95% confidence interval: 1.01-20.4).
CONCLUSIONS
ALT <21 IU/L at 1 year after NA initiation has a lower risk of HCC and could be used as a target value for NA treatment.
目的
丙氨酸氨基转移酶（ALT）是开始使用核苷酸/核苷类似物（NA）的一项标准，且NA治疗可使ALT水平降低。然而，治疗后ALT水平与肝细胞癌（HCC）风险之间的关联仍不明确。为填补这一空白，我们旨在确定NA治疗期间ALT水平的目标值。
方法
总共纳入了413例接受恩替卡韦、替诺福韦艾拉酚胺或富马酸替诺福韦二吡呋酯治疗的慢性乙型肝炎患者。对随后HCC的发生情况进行检查，并评估NA治疗期间作为HCC风险标志物的ALT水平目标值。
结果
中位随访时间为5.1年，在此期间27例患者（8.6%）发生了HCC。治疗开始时的ALT水平与HCC发生无关（p = 0.08）。按NA起始治疗1年后的ALT进行分层时，ALT≥21 IU/L患者的HCC累积3年和5年发生率分别为11.5%和18.1%，而ALT<21 IU/L患者的分别为2.3%和6.5%。与ALT≥21 IU/L的患者相比，ALT<21 IU/L的患者发生HCC的风险显著更低（p = 0.002）。在对年龄、性别和血小板计数进行校正的多变量分析中，ALT≥21 IU/L是HCC发生的独立危险因素，风险比为4.5（95%置信区间：1.01 - 20.4）。
结论
NA起始治疗1年后ALT<21 IU/L发生HCC的风险较低，可作为NA治疗的目标值。
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