Volume 98, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



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 and 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% ( = 107/861), whereas elevated alanine transaminase (ALT) and aspartate transaminase levels were observed in 15.1% ( = 130/861) and 14.8% ( = 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% ( = 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.

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


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Jain A, Kaushik R, Kaushik RM, , 2016. Malarial hepatopathy: clinical profile and association with other malarial complications. Acta Trop 159: 95105. [Google Scholar]
  2. Anand AC, Ramji C, Narula AS, Singh W, , 1992. Malarial hepatitis: a heterogeneous syndrome? Natl Med J India 5: 5962. [Google Scholar]
  3. Mehta SR, Naidu G, Chandar V, Singh IP, Johri S, Ahuja RC, , 1989. Falciparum malaria—present day problems. An experience with 425 cases. J Assoc Physicians India 37: 264267. [Google Scholar]
  4. Murthy GL, Sahay RK, Sreenivas DV, Sundaram C, Shantaram V, , 1998. Hepatitis in falciparum malaria. Trop Gastroenterol 19: 152154. [Google Scholar]
  5. Mazumder R, Mishra RK, Mazumder H, Mukherjee P, , 2002. Jaundice in falciparum malaria—some prospective observations. J Indian Med Assoc 100: 312314. [Google Scholar]
  6. Wilairatana P, Looareesuwan S, Charoenlarp P, , 1994. Liver profile changes and complications in jaundiced patients with falciparum malaria. Trop Med Parasitol 45: 298302. [Google Scholar]
  7. Ramachandran S, Perera MV, , 1976. Jaundice and hepatomegaly in primary malaria. J Trop Med Hyg 79: 207210. [Google Scholar]
  8. Hazra BR, Chowdhury RS, Saha SK, Ghosh MB, Mazumder AK, , 1998. Changing scenario of malaria: a study at Calcutta. Indian J Malariol 35: 111116. [Google Scholar]
  9. Tangpukdee N, Thanachartwet V, Krudsood S, Luplertlop N, Pornpininworakij K, Chalermrut K, Phokham S, Kano S, Looareesuwan S, Wilairatana P, , 2006. Minor liver profile dysfunctions in Plasmodium vivax, P. malariae and P. ovale patients and normalization after treatment. Korean J Parasitol 44: 295302. [Google Scholar]
  10. Mishra SK, Mohanty S, Das BS, Patnaik JK, Satpathy SK, Mohanty D, Bose TK, , 1992. Hepatic changes in P. falciparum malaria. Indian J Malariol 29: 167171. [Google Scholar]
  11. Gupta UC, Kataria ML, , 1993. Plasmodium falciparum hepatitis during malaria epidemic. J Assoc Physicians India 41: 292. [Google Scholar]
  12. Kochar DK, Agarwal P, Kochar SK, Jain R, Rawat N, Pokharna RK, Kachhawa S, Srivastava T, , 2003. Hepatocyte dysfunction and hepatic encephalopathy in Plasmodium falciparum malaria. QJM 96: 505512. [Google Scholar]
  13. Abro AH, Ustadi AM, Abro HA, Abdou AS, Younis NJ, Akaila SI, , 2009. Jaundice with hepatic dysfunction in P. falciparum malaria. J Coll Physicians Surg Pak 19: 363366. [Google Scholar]
  14. Patwari A, Aneja S, Berry A, Ghosh S, , 1979. Hepatic dysfunction in childhood malaria. Arch Dis Child 54: 139141. [Google Scholar]
  15. Anand AC, Puri P, , 2005. Jaundice in malaria. J Gastroenterol Hepatol 20: 13221332. [Google Scholar]
  16. Kochar DK, Kaswan K, Kochar SK, Sirohi P, Pal M, Kochar A, Agrawal RP, Das A, , 2006. A comparative study of regression of jaundice in patients of malaria and acute viral hepatitis. J Vector Borne Dis 43: 123129. [Google Scholar]
  17. Fazil A, Vernekar PV, Geriani D, Pant S, Senthilkumaran S, Anwar N, Prabhu A, Menezes RG, , 2013. Clinical profile and complication of malaria hepatopathy. J Infect Public Health 6: 383388. [Google Scholar]
  18. Saya RP, Debabrata G, Saya GK, , 2012. Malarial hepatopathy and its outcome in India. N Am J Med Sci 4: 449. [Google Scholar]
  19. Bhalla A, Suri V, Singh V, , 2006. Malarial hepatopathy. J Postgrad Med 52: 315320. [Google Scholar]
  20. Temple R, , 2006. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf 15: 241243. [Google Scholar]
  21. Bag S, Samal GC, Deep N, Patra UC, Nayak M, Meher LK, , 1994. Complicated falciparum malaria. Indian Pediatr 31: 821825. [Google Scholar]
  22. Shah S, Ali L, Sattar RA, Aziz T, Ansari T, Ara J, , 2009. Malarial hepatopathy in falciparum malaria. J Coll Physicians Surg Pak 19: 367370. [Google Scholar]
  23. Kachawaha S, Pokharana R, Rawat N, Garg P, Badjatiya H, Kochar DK, , 2003. Ultrasonography in malarial hepatitis. Indian J Gastroenterol 22: 110. [Google Scholar]
  24. Chawla LS, Sidhu G, Sabharwal BD, Bhatia KL, Sood A, , 1989. Jaundice in Plasmodium falciparum. J Assoc Physicians India 37: 390391. [Google Scholar]
  25. Joshi YK, Tandon BN, Acharya SK, Babu S, Tandon M, , 1986. Acute hepatic failure due to Plasmodium falciparum liver injury. Liver 6: 357360. [Google Scholar]
  26. McMahon AE, Kelsey JE, Derauf DE, , 1954. Hepatitis of malarial origin: clinical and pathologic study of fifty-four Korean veterans. AMA Arch Intern Med 93: 379386. [Google Scholar]
  27. Kleeberg J, Birnbaum D, , 1948. Studies on liver damage in acute malaria. Trans R Soc Trop Med Hyg 41: 555566. [Google Scholar]
  28. Silva-Pinto A, Ruas R, Almeida F, Duro R, Silva A, Abreu C, Sarmento A, , 2017. Artemether–lumefantrine and liver enzyme abnormalities in non-severe Plasmodium falciparum malaria in returned travellers: a retrospective comparative study with quinine-doxycycline in a Portuguese centre. Malar J 16: 43. [Google Scholar]
  29. McCarthy JS, 2016. A phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study. Malar J 15: 469. [Google Scholar]
  30. Griffin P, 2016. Safety and reproducibility of a clinical trial system using induced blood stage Plasmodium vivax infection and its potential as a model to evaluate malaria transmission. PLoS Negl Trop Dis 10: e0005139. [Google Scholar]
  31. Nyunt MM, Hendrix CW, Bakshi RP, Kumar N, Shapiro TA, , 2009. Phase I/II evaluation of the prophylactic antimalarial activity of pafuramidine in healthy volunteers challenged with Plasmodium falciparum sporozoites. Am J Trop Med Hyg 80: 528535. [Google Scholar]
  32. Epstein JE, Rao S, Williams F, Freilich D, Luke T, Sedegah M, de la Vega P, Sacci J, Richie TL, Hoffman SL, , 2007. Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. J Infect Dis 196: 145154. [Google Scholar]
  33. Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC, , 2006. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 296: 8793. [Google Scholar]
  34. WHO Offset Publication, 1979. WHO Handbook for Reporting Results of Cancer Treatment. Geneva, Switzerland: World Health Organization, 48, 16–21.
  35. Antoine DJ, 2013. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 58: 777787. [Google Scholar]
  36. Seixas E, Oliveira P, Moura Nunes JF, Coutinho A, , 2008. An experimental model for fatal malaria due to TNF-alpha-dependent hepatic damage. Parasitology 135: 683690. [Google Scholar]
  37. Seixas E, 2009. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci USA 106: 1583715842. [Google Scholar]
  38. Oliveira-Lima OC, Bernardes D, Xavier Pinto MC, Esteves Arantes RM, Carvalho-Tavares J, , 2013. Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection. Microbes Infect 15: 903910. [Google Scholar]
  39. Dey S, Mazumder S, Siddiqui AA, Iqbal MS, Banerjee C, Sarkar S, De R, Goyal M, Bindu S, Bandyopadhyay U, , 2014. Association of heme oxygenase 1 with the restoration of liver function after damage in murine malaria by Plasmodium yoelii. Infect Immun 82: 31133126. [Google Scholar]
  40. Guha M, Kumar S, Choubey V, Maity P, Bandyopadhyay U, , 2006. Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J 20: 12241226. [Google Scholar]
  41. Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L, , 2013. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J 12: 70. [Google Scholar]

Data & Media loading...

Supplemental Figure and Table

  • Received : 29 Sep 2017
  • Accepted : 20 Dec 2017
  • Published online : 12 Feb 2018

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error