title: Patterns and causes of liver involvement in acute dengue infection.
abstract: Liver involvement in acute dengue infection is frequently observed and sometimes leads to acute liver failure, with fatal outcomes. Many factors are thought to contribute to liver dysfunction, including hypoxic injury due to decreased perfusion, direct damage by the virus and immune mediated injury. In this study, we sought to identify the pattern in the change in liver enzymes throughout the illness and its association with the degree of viraemia, onset and extent of plasma leakage and inflammatory mediators.
  
  
  
  Serial daily blood samples were obtained from 55 adult patients with acute dengue from the time of admission to discharge and the liver function tests, viral loads and cytokines were assessed. The onset and extent of fluid leakage was measured by daily ultrasound examinations and all clinical and laboratory features were serially recorded.
  
  
  
  Aspartate transaminase (AST), alanine transaminase (ALT) and gamma glutamyl transferase (GGT) levels were elevated in patients with dengue infection throughout the illness. The highest AST levels were seen on day 6 of illness and both AST and GGT levels were significantly higher in patients with severe dengue (SD), when compared to those with non-severe dengue (NSD) on day 5 and 6 of illness. Three patients with SD had AST and ALT values of >1000/IU in the absence of any fluid leakage or a rise in the haematocrit (≥20 %). The peak of the AST levels and the lowest serum albumin levels were seen 24 h before the maximum fluid leakage and 24 h after the peak in viraemia. Both serum IL-10 and IL-17 levels were elevated during early illness and were significantly higher in those with SD when compared to NSD.
  
  
  
  Dengue associated liver injury appears to peak around day 6 and 7. Therefore, liver function tests done at earlier dates might not reflect the extent of liver involvement in acute infection. Since severe liver involvement can occur in the absence of fluid leakage, after the peak viraemia, and since it is associated with high IL-17 and IL-10 levels, possible immune mechanisms leading to hepatic damage should be investigated.
authors.affiliation: Department of Microbiology, Centre for Dengue Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: Samitha
authors.initials: S
authors.lastname: Fernando
authors.affiliation: Infectious Diseases Hospital, Angoda, Sri Lanka.
authors.forename: Ananda
authors.initials: A
authors.lastname: Wijewickrama
authors.affiliation: Department of Microbiology, Centre for Dengue Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: Laksiri
authors.initials: L
authors.lastname: Gomes
authors.affiliation: Department of Microbiology, Centre for Dengue Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: Chameera T
authors.initials: CT
authors.lastname: Punchihewa
authors.affiliation: Department of Microbiology, Centre for Dengue Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: S D P
authors.initials: SD
authors.lastname: Madusanka
authors.affiliation: Department of Anatomy, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: Harsha
authors.initials: H
authors.lastname: Dissanayake
authors.affiliation: Department of Family Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: Chandima
authors.initials: C
authors.lastname: Jeewandara
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka.
authors.forename: Hemantha
authors.initials: H
authors.lastname: Peiris
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford NIHR Biomedical Research Centre and University of Oxford, Oxford, OX3 9DS, UK.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
authors.affiliation: Department of Microbiology, Centre for Dengue Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka. gathsaurie.malavige@ndm.ox.ac.uk.|MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford NIHR Biomedical Research Centre and University of Oxford, Oxford, OX3 9DS, UK. gathsaurie.malavige@ndm.ox.ac.uk.
authors.forename: Gathsaurie Neelika
authors.initials: GN
authors.lastname: Malavige
mesh_terms: D000208:Acute Disease; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D008107:Liver Diseases / Q000097:blood / Q000821:virology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis; D019595:Severe Dengue / Q000097:blood / Q000150:complications* / Q000821:virology; D019562:Viral Load; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D020381:Interleukin-17; D012709:Serum Albumin; D016753:Interleukin-10; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Dengue; Fluid leakage; Immune mediated; Liver injury; Transaminases; Viral loads