The Dynamics of Liver Function Test Abnormalities after Malaria Infection: A Retrospective Observational Study

Liver dysfunction has long been recognized as a clinical feature of malaria. We have observed delayed elevation in the transaminase portion of liver function tests (LFTs) after treatment in some participants undergoing induced blood stage malaria infection. We sought to determine whether similar LFT elevations occur after naturally acquired infection. We performed a retrospective audit of confirmed cases of Plasmodium falciparum and Plasmodium vivax in Queensland, Australia, from 2006 to 2016. All LFT results from malaria diagnosis until 28 days after diagnosis were collected with demographic and clinical information to describe longitudinal changes. The timing of peak LFT elevations was classified as early (0-3 days), delayed (4-11 days), or late (12-28 days) with respect to the day of diagnosis. Among 861 cases with LFT evaluated, an elevated bilirubin level was identified in 12.4% (N = 107/861), whereas elevated alanine transaminase (ALT) and aspartate transaminase levels were observed in 15.1% (N = 130/861) and 14.8% (N = 127/861) of cases, respectively. All peak bilirubin results occurred in the early period, whereas ALT elevations were biphasic, with elevations in the early and delayed periods, with 35.4% (N = 46/130) of cases delayed. Univariate and paired stepwise logistic regression analyses were performed to investigate factors associated with the incidence and timing of transaminase elevation. A raised ALT level at diagnosis was strongly associated with the timing of transaminase elevation. No other demographic, parasitic, or treatment factors were associated. Liver function test abnormalities are likely an inherent although variable aspect of human malaria, and individual-specific factors may confer susceptibility to hepatocyte injury.