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

Date Published: April 12, 2018

Publisher: The American Society of Tropical Medicine and Hygiene

Author(s): John Woodford, G. Dennis Shanks, Paul Griffin, Stephan Chalon, James S. McCarthy.


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.

Partial Text

Abnormalities in liver function have been described but relatively little investigated compared with other aspects of clinical malaria. Reporting of malaria-associated liver injury in the literature is heterogeneous and primarily focused on biochemical measurement of liver function tests (LFTs), such as bilirubin and the transaminases alanine transaminase (ALT) and aspartate transaminase (AST). There are few thorough longitudinal descriptions of malaria-associated liver injury.

In this audit, we have identified rates of elevated bilirubin and malarial hepatopathy consistent with other reports.1–3,8,9 These abnormalities are transient, more frequently observed in P. falciparum infection than in other Plasmodium species, and may vary widely in severity (up to > 25 × ULN). We have also identified a relatively large proportion of cases with elevated transaminases after diagnosis and treatment that has not been well described previously in the naturally acquired malaria literature. Although elevations in bilirubin levels appear to peak and resolve soon after treatment, peak transaminase elevations may not occur simultaneously. This may represent malaria-associated liver effects after hemolysis, which could explain the progressive increase in the ALT/AST ratio observed with time for all cases, as the hemolysis-related AST level decreases while the hepatocyte-specific ALT level increases.

Liver function test abnormalities occur commonly in persons infected with various plasmodia and are likely an inherent although variable aspect of human malaria. Elevated transaminase levels due to malaria are transient, may be delayed beyond antimalarial treatment, and may not occur simultaneously with bilirubin changes. No clinical or demographic factors are clearly related to transaminase elevation; however, extrapolation of mouse-model studies may suggest that individual variation in inflammatory response and the efficiency of heme breakdown could play a role in transaminase elevation.




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