image of Liver Function Test Abnormalities in Experimental and Clinical Plasmodium vivax Infection
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human VISs where subjects were treated with chloroquine ( = 24) or artefenomel ( = 8) and compared them with studies in Thailand ( = 41) and Malaysia ( = 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 posttreatment. 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; = 0.02) for every log 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; = 0.06), this risk disappeared when corrected for parasite clearance burden (PCB). Peak ALT also correlated with peak C-reactive protein ( = 0.44; = 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 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.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  • Received : 16 May 2020
  • Accepted : 05 Jul 2020
  • Published online : 17 Aug 2020
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