Liver Function Test Abnormalities in Experimental and Clinical Plasmodium vivax Infection.
Liver Function Test Abnormalities in Experimental and Clinical Plasmodium vivax Infection.
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DOI：
10.4269/ajtmh.20-0491
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
McCarthy JS
中科院分区：
文献类型：
--
作者：
Odedra A;Webb L;Marquart L;Britton LJ;Chalon S;Moehrle JJ;Anstey NM;William T;Grigg MJ;Lalloo DG;Barber BE;McCarthy JS
疟疾志愿者感染研究（VIS）中治疗后肝脏转氨酶升高引起了安全问题。我们调查了两名接受氯喹 (n = 24) 或阿替诺梅尔 (n = 8) 治疗的人类间日疟原虫 VIS 的转氨酶升高情况，并将其与泰国 (n = 41) 和马来西亚 (n = 76) 的研究进行了比较。在 VIS 中，11/32 (34%) 志愿者的丙氨酸转氨酶 (ALT) 升高至 ≥ 2.5 × 正常上限 (ULN)，并在治疗后 5-8 天达到峰值。转氨酶升高是无症状的，与胆红素升高无关，并在第 42 天解决。寄生虫清除负担 (PCB) 每增加 log10（定义为对数倍减少），ALT ≥ 2.5 × ULN 的风险增加超过 4 倍（比值比 [OR] 4.28；95% CI：1.26–14.59；P = 0.02）治疗后 24 小时出现寄生虫血症。尽管阿替诺梅尔治疗后 ALT 升高 ≥ 2.5 × ULN 比氯喹治疗后更常见（5/8 [63%] 对比 6/24 [25%]；OR 5.0；95% CI：0.91–27.47；P = 0.06），但在校正 PCB 后，这种风险消失了。 ALT 峰值还与 C 反应蛋白峰值相关（R = 0.44；P = 0.012）。在疟疾流行地区，ALT 升高（≥ 2.5 × ULN）不太常见，接受阿替诺梅尔治疗的泰国患者中有 1/41 (2.5%) 出现这种情况，而接受氯喹或青蒿素联合治疗的 76 名马来西亚患者中没有出现这种情况。治疗后转氨酶升高在实验性间日疟原虫感染中很常见，但似乎不会影响参与者的安全。尽管这些变化的机制仍不确定，但宿主对寄生虫清除的炎症反应可能有所贡献。
Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5–8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26–14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91–27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.
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DOI：
10.1073/pnas.1414221111
发表时间：
2014-12-16
影响因子：
11.1
作者：
Belen Jimenez-Diaz, Maria;Ebert, Daniel;Guy, R. Kiplin
通讯作者：
Guy, R. Kiplin
影响因子：
15.9
作者：
Collins, Katharine A.;Wang, Claire Y. T.;McCarthy, James S.
通讯作者：
McCarthy, James S.
影响因子：
3.8
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Griffin P;Pasay C;Elliott S;Sekuloski S;Sikulu M;Hugo L;Khoury D;Cromer D;Davenport M;Sattabongkot J;Ivinson K;Ockenhouse C;McCarthy J
通讯作者：
McCarthy J
影响因子：
--
作者：
Barrett, PJ;Emmins, PD;Bradley, DJ
通讯作者：
Bradley, DJ
影响因子：
11.8
作者：
Gasasira, Anne F.;Kamya, Moses R.;Dorsey, Grant
通讯作者：
Dorsey, Grant