Factors leading to liver injury in acute dengue infection

Background: Liver damage is commonly seen in dengue infection, which can sometimes lead to acute liver failure. Although the exact causes of liver injury is unknown, direct viral injury, hypoxic injury due to vascular leakage and immune mediated liver damage are thought to contribute to liver involvement in dengue. Therefore, we proceeded to investigate the patterns of liver injury and the possible contributing factors in acute dengue infection. Methods & Materials: 55 adult patients with confirmed acute dengue infection were recruited during day 3 -5 of the illness and serial recordings of liver function tests, viral loads, serum IL10 and IL17 levels and the extent of fluid leakage were measureddaily until discharge from hospital. According to the 2011 WHO guidelines, 19 of these patients were classified as dengue haemorrhagic fever (DHF) and 36 were classified as dengue fever (DF). Results: Serum alanine transaminase (ALT), aspartate transaminase (AST), conjugated and unconjugated bilirubin, gamma glutamyl transaminase and alkaline phosphatase levels were highest on day 7 of illness in patients with DHF and DF. Serum albumin levels were only lower in patients with DHF. The peak in liver enzymes occurred 2 days after the peak of viraemia in patients with DHF and DF. The extent of the rise in liver enzymes did not correlate with the extent of vascular leak and there were no significant differences in any of the liver enzymes between patients with DF or DHF. In contrast, IL-17 levels were significantly associated with ALT levels (p = 0.02, Spearmans r = 0.17). IL-17 levels were significantly higher (p = 0.008) on day 5 of illness in patients with ALT levels > 4 times the upper limit of normal (mean 38.2 SE ± 10.1), when compared to those with lesser degree of liver involvement (10.3, SE ± 10.2). Although IL-10 were higher in patients with higher AST levels, this was not significant. Conclusion: Dengue associated liver injury appears to peak at day 7 of illness and appears to associate with serum IL-17 levels but not with the degree of fluid leakage or viraemia. Since IL17 was also shown to cause liver injury in dengue mice models, the mechanisms by which this occurs needs to be further investigated.