Hepatic changes in fatal malaria: an emerging problem

Over the last few years there has been a rise in the incidence of fatal malaria in urban areas of India, and this worrying trend is a major cause of concern for the national health authorities. The spectrum of histopathological changes that occur in the livers of Indian subjects with fatal malaria has recently been investigated, in a retrospective autopsy-based study. This investigation involved the 151 fatal cases of malaria seen at a tertiary-care hospital in Mumbai between January 2001 and December 2007. The diagnosis of malaria was made on the basis of the examination of a smear of peripheral blood (81 cases) or a histopathological examination (70 cases). For each subject of the present study, at least two blocks were prepared, using routine histological methods, from a liver sample collected at autopsy. The sections produced from these blocks were stained with various compounds, including Prussian Blue (which was used to distinguish malarial pigment from non-malarial). The pattern of liver necrosis seen in the malaria cases was compared with that seen in 11 cases of acute viral hepatitis, and with the liver histology seen in 50 control subjects, who had died of causes other than malaria or liver disease. The most common clinical presentation of the subjects who died of malaria was fever (85%), followed by jaundice (68%). The presence of jaundice often led to an initial misdiagnosis of acute viral hepatitis. In the livers of the fatal malaria cases, Kupffer-cell hyperplasia and the retention of haemozoin pigment were the two most common histological features. Necrosis was seen in 63 (41%) of these cases, with predominant centrilobular haemorrhagic necrosis in 16 (10%). The inflammation in the sections of liver from the malaria cases with hepatic necrosis was sparse compared with that in the corresponding sections from patients with acute viral hepatitis, although mixed portal inflammation was frequently noted in the malaria cases. None of the liver sections from the 50 control subjects showed evidence of pigment, necrosis or any other pathology. In conclusion, jaundice was one of the commonest clinical presentations of the fatal cases of malaria and could mimic viral hepatitis on clinical examination. The characteristic histopathological features of the livers of those with fatal malaria were Kupffer-cell hyperplasia, malarial pigment within the Kupffer cells, and liver-cell necrosis, with portal inflammation, steatosis and cholestasis also observed.