正常的治疗ALT与乙型肝炎中减少的肝脏事件有关

StephenW

Madeline Morr, Associate Editor
June 21, 2018
Normal on-Treatment ALT Linked to Reduced Hepatic Events in Hepatitis B

The cumulative incidence of composite hepatic events at 6 years was 3.51% in ALT-N and 5.70% in no ALT-N group.
The cumulative incidence of composite hepatic events at 6 years was 3.51% in ALT-N and 5.70% in no ALT-N group.

Patients with chronic hepatitis B (CHB) have a lower risk of hepatic events if they achieve normal on-treatment alanine aminotransferase (ALT) in the first 12 months of nucleos(t)ide analogue (NA) treatment, according to a study published in the Journal of Hepatology.

Grace Lai-Hung Wong, MBChB, MD, FRCP, FHKCP, FHKAM, from the Institute of Digestive Disease at the Chinese University of Hong Kong, and colleagues, performed a retrospective territory-wide cohort study to evaluate the impact of normal on-treatment ALT at different time points at the first year of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment in patients with CHB. The researchers used data from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority (HA), Hong Kong. Patients with CHB who received ETV and/or TDF from January 1, 2005, to December 31, 2016, in Hong Kong were included. Patients were followed until death or last day with dispensed ETV or TDF within 6 years from the baseline visit.

Baseline date was defined as the date of the first prescription of ETV or TDF. 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 outcome were composite hepatic events (including hepatocellular carcinoma) based on diagnosis codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded.

A total of 46,441 ETV- and/or TDF-treated patients were identified, among whom 21,182 patients with CHB fulfilled the inclusion and exclusion criteria and were included in the analysis. A total of 10,437 patients achieved normal on-treatment ALT within 12 months of NA treatment. The rate of normal on-treatment ALT at 12 months was lower in patients receiving TDF alone (1,119/2,709, 41.3%) than in those receiving ETV alone (9,306/18,447, 50.5%).


Patients with and without ALT-N differed in baseline ALT (58 vs 61 U/L), HBV 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 with 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 co-variates, with adjusted hazard ratios (95% CI) of 0.61, 0.55, 0.54, and 0.51, respectively. The cumulative incidence of composite hepatic events at 6 years was 3.51% in ALT-N and 5.70% in no ALT-N group.

“In conclusion, patients with CHB would have a lower risk of hepatic events if they achieve normal on-treatment ALT in the first 12 months of NA treatment,” the authors stated. “The higher the ALT levels during treatment, the higher the risk of hepatic events. The impact of specific NA on normal on-treatment ALT warrants further study.”
Reference

Wong GL, Chan HL, Tse YK, et al. Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B [published online May 11 2018]. J Hepatol. doi: 10.1016/j.jhep.2018.05.009

桦子

Madeline Morr，副编辑
2018年6月21日
正常的治疗ALT与乙型肝炎中减少的肝脏事件有关

6年时ALT复合性肝病事件累计发生率为3.51％，无ALT-N组为5.70％。
6年时ALT复合性肝病事件累计发生率为3.51％，无ALT-N组为5.70％。

根据发表在美国国家科学院院刊上的一项研究，慢性乙型肝炎（CHB）患者如果在核苷（酸）类似物（NA）治疗的头12个月内达到正常的治疗丙氨酸转氨酶（ALT） “肝脏病学杂志”。

香港中文大学消化疾病研究所的Grace Lai-Hung Wong，MBCHB，医学博士，FRCP，FHKCP，FHKAM及其同事进行了一项回顾性的全港性队列研究，以评估正常治疗的影响在慢性乙型肝炎患者恩替卡韦（ETV）或替诺福韦二吡呋酯富马酸（TDF）治疗的第一年不同时间点的ALT。研究人员使用了香港医院管理局（医管局）的临床资料分析和报告系统（CDARS）的数据。包括从2005年1月1日至2016年12月31日在香港接受ETV和/或TDF的CHB患者。在基线访视后的6年内，患者接受直至死亡或最后一天的分发ETV或TDF。

基准日期被定义为ETV或TDF的第一次处方的日期。收集并分析系列治疗中的ALT水平。正常治疗前ALT（ALT-N）定义为男性ALT <30U / L，女性<19U / L。主要和次要结局是基于诊断编码的复合肝事件（包括肝细胞癌）。在第一年抗病毒治疗或随访<1年之前或期间发生肝脏事件的患者被排除在外。

共鉴定了46,441名ETV和/或TDF治疗的患者，其中21,182名CHB患者符合纳入和排除标准并纳入分析。在NA治疗的12个月内共有10437名患者达到正常的治疗ALT。仅接受TDF治疗的患者在12个月时的正常治疗ALT率较低（1,119 / 2,709,41.3％）低于仅接受ETV治疗的患者（9,306 / 18,447，50.5％）。


基线ALT（58 vs 61 U / L），HBV DNA（4.9 vs 5.1 log10 IU / mL）和肝硬化状态（8.8％比10.5％）与ALT-N无关。共有627例（3.0％）患者发生复合性肝病事件。与没有ALT-N相比，调整基线ALT和其他重要协变量后3,6,9和12个月的ALT-N降低了肝病事件的风险，调整后的危险比（95％CI）为0.61 ，0.55,0.54和0.51。 6年时ALT复合性肝病事件累计发生率为3.51％，无ALT-N组为5.70％。


“作为结论，CHB患者如果在NA治疗的前12个月内达到正常的治疗ALT，他们的肝脏事件风险会更低。”作者们表示。 “治疗期间ALT水平越高，肝脏事件的风险就越高。 具体NA对正常治疗ALT的影响值得进一步研究。“
参考

  Wong GL，Chan HL，Tse YK等人。 在抗病毒治疗期间正常的治疗中ALT与慢性乙型肝炎患者的肝脏事件风险较低相关[2018年5月11日在线发表]。 J Hepatol。 doi：10.1016 / j.jhep.2018.05.009