Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
J Hepatol. 2018 Oct;69(4):793-802. doi: 10.1016/j.jhep.2018.05.009.
BACKGROUND & AIMS: Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB).
A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005-2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded.
A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ± 1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49-0.77), 0.55 (0.45-0.67), 0.54 (0.44-0.65) and 0.51 (0.42-0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%-6.32%) in the no ALT-N group (p <0.001).
Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients.
We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events.
最近的研究表明，不同核苷（酸）类似物（NAs）治疗中正常的治疗后丙氨酸氨基转移酶（ALT）水平出现不同的比率；但其临床意义尚不清楚。我们旨在评估恩替卡韦（ETV）或替诺福韦酯富马酸（TDF）治疗慢性乙型肝炎（CHB）患者治疗中正常的治疗后 ALT 对其的影响。
在 2005-2016 年，确定了一个接受 ETV 和/或 TDF 治疗的 CHB 患者的全港队列。收集并分析了连续的治疗后 ALT 水平。治疗后正常 ALT（ALT-N）定义为男性 ALT <30U/L，女性 ALT <19U/L。主要和次要结局是根据诊断代码确定的复合肝脏事件（包括肝细胞癌）。排除抗病毒治疗前或治疗后 1 年内或随访 <1 年的有肝事件的患者。
共确定了 21182 例 CHB 患者（10437 例在抗病毒治疗 12 个月后 ALT-N，10745 例无 ALT-N），并随访了 4.0±1.7 年。有和无 ALT-N 的患者在基线 ALT（58 vs. 61U/L）、乙型肝炎病毒 DNA（4.9 vs. 5.1 log10 IU/ml）和肝硬化状态（8.8% vs. 10.5%）方面存在差异。共有 627 例（3.0%）患者发生了复合肝脏事件。与无 ALT-N 相比，治疗后 3、6、9 和 12 个月的 ALT-N 降低了肝脏事件的风险，调整基线 ALT 和其他重要协变量后，调整后的危险比（95%CI）分别为 0.61（0.49-0.77）、0.55（0.45-0.67）、0.54（0.44-0.65）和 0.51（0.42-0.61）（均 p<0.001）。在 ALT-N 组中，六年时复合肝脏事件的累积发生率（95%CI）为 3.51%（3.06%-4.02%），而在无 ALT-N 组中为 5.70%（5.15%-6.32%）（p<0.001）。
在接受 NA 治疗的 CHB 患者中，治疗后正常的 ALT 与较低的肝脏事件风险相关，这转化为这些患者的临床结局改善。
我们研究了 21182 例接受抗病毒治疗的慢性乙型肝炎患者。丙氨酸氨基转移酶是肝功能的实验室标志物，升高表明肝功能障碍，在严重情况下提示肝炎。CHB 患者治疗中第一年的正常治疗后丙氨酸氨基转移酶与较低的肝脏事件风险相关。
