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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Extensive haemorrhagic necrosis of liver is an unpredictable fatal complication in dengue infection: a postmortem study

Authors: SAM Kularatne, IVB Imbulpitiya, RA Abeysekera, RN Waduge, RPVJ Rajapakse, KGAD Weerakoon

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Dengue infection carries a potential risk of death despite stringent management of plasma leak and haemorrhage. It appears that the extent of liver dysfunction determines the outcome.

Methods

We present a postmortem study of five patients, died of dengue shock syndrome who had markedly elevated liver enzymes and irreparable circulatory failure.

Results

All were females with a median age of 46 years (range 20–50 years). All had positive NS1 and IgM. Clinically, one patient developed severe degree of hepatic encephalopathy whilst three patients developed uncontrollable bleeding manifestations. Dengue virus was detected in three liver specimens by reverse transcription PCR. Histology of the liver revealed massive necrosis with haemorrhages in these patients with evidence of micro and macrovesicular steatosis with significant periportal inflammatory infiltrate. No significant ischaemic changes or necrosis was observed in the other organs.

Conclusions

Severe haemorrhagic necrosis of the liver was the cause of death in these patients probably due to direct viral infection. Predilection for severe liver disease remains unknown. Therefore, it is prudent to think beyond plasma leak as the main pathology of dengue infection and attempts should be made to develop other treatment modalities to prevent and manage unforeseen fatal complications of dengue infection.
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Literature
1.
go back to reference WHO: Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011, World Health Organization WHO: Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. 2011, World Health Organization
2.
go back to reference Annual Health Bulletin. 2010, Sri Lanka: Ministry of Health Annual Health Bulletin. 2010, Sri Lanka: Ministry of Health
3.
go back to reference Havens WP: Hepatitis, yellow fever and dengue. Annu Rev Microbiol. 1954, 8: 289-310. 10.1146/annurev.mi.08.100154.001445.CrossRefPubMed Havens WP: Hepatitis, yellow fever and dengue. Annu Rev Microbiol. 1954, 8: 289-310. 10.1146/annurev.mi.08.100154.001445.CrossRefPubMed
4.
go back to reference Weerakoon KG, Kularatne SA, Edussuriya DH, Kodikara SK, Gunatilake LP, Pinto VG, Seneviratne AB, Gunasena S: Histopathological diagnosis of myocarditis in a dengue outbreak in Sri Lanka, 2009. BMC Res Notes. 2011, 4: 268-10.1186/1756-0500-4-268.CrossRefPubMedPubMedCentral Weerakoon KG, Kularatne SA, Edussuriya DH, Kodikara SK, Gunatilake LP, Pinto VG, Seneviratne AB, Gunasena S: Histopathological diagnosis of myocarditis in a dengue outbreak in Sri Lanka, 2009. BMC Res Notes. 2011, 4: 268-10.1186/1756-0500-4-268.CrossRefPubMedPubMedCentral
5.
go back to reference Malavige GN, Fernando N, Ogg G: Pathogenesis of dengue viral infections. Sri Lanka J Infect Dis. 2011, 1: 2-8. Malavige GN, Fernando N, Ogg G: Pathogenesis of dengue viral infections. Sri Lanka J Infect Dis. 2011, 1: 2-8.
6.
go back to reference de Marcedo FC, Nicol AF, Cooper LD, Yearsley M, Pires AR, Nuovo GJ: Histologic, viral and molecular correlates of dengue fever infection of the liver using highly sensitive immunohistochemistry. Diagn Mol Pathol. 2006, 15: 223-228. 10.1097/01.pdm.0000213462.60645.cd.CrossRef de Marcedo FC, Nicol AF, Cooper LD, Yearsley M, Pires AR, Nuovo GJ: Histologic, viral and molecular correlates of dengue fever infection of the liver using highly sensitive immunohistochemistry. Diagn Mol Pathol. 2006, 15: 223-228. 10.1097/01.pdm.0000213462.60645.cd.CrossRef
7.
go back to reference Guidelines on management of dengue fever and dengue haemorrhagic fever in adults. 2012, Sri Lanka: Ministry of Health, National guidelines Guidelines on management of dengue fever and dengue haemorrhagic fever in adults. 2012, Sri Lanka: Ministry of Health, National guidelines
8.
go back to reference Trung DT, Thao LTT, Hien TT, Hung NT, Vinh NN, Hein PTD, Ching NT, Simmons C, Wills B: Liver involvement associated with dengue infection in adults in Vietnam. Am J Trop Med Hyg. 2010, 83 (4): 774-780. 10.4269/ajtmh.2010.10-0090.CrossRefPubMedPubMedCentral Trung DT, Thao LTT, Hien TT, Hung NT, Vinh NN, Hein PTD, Ching NT, Simmons C, Wills B: Liver involvement associated with dengue infection in adults in Vietnam. Am J Trop Med Hyg. 2010, 83 (4): 774-780. 10.4269/ajtmh.2010.10-0090.CrossRefPubMedPubMedCentral
9.
go back to reference Kularatne SA, Gawarammana IB, Kumarasiri PR: Epidemiology, clinical features, laboratory investigations and early diagnosis of dengue fever in adults: a descriptive study in Sri Lanka. Southeast Asian J Trop Med Public Health. 2005, 36: 686-692.PubMed Kularatne SA, Gawarammana IB, Kumarasiri PR: Epidemiology, clinical features, laboratory investigations and early diagnosis of dengue fever in adults: a descriptive study in Sri Lanka. Southeast Asian J Trop Med Public Health. 2005, 36: 686-692.PubMed
10.
go back to reference Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV: Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol. 1992, 30: 545-551.PubMedPubMedCentral Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV: Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol. 1992, 30: 545-551.PubMedPubMedCentral
11.
go back to reference Larreal Y, Valero N, Estevez J, Reyes I, Maldonado M, Espina LM, Arias J, Melean E, Ariez G, Atencio R: Hepatic alterations in patients with dengue. Invest Clin. 2005, 46 (2): 169-178.PubMed Larreal Y, Valero N, Estevez J, Reyes I, Maldonado M, Espina LM, Arias J, Melean E, Ariez G, Atencio R: Hepatic alterations in patients with dengue. Invest Clin. 2005, 46 (2): 169-178.PubMed
12.
go back to reference Kuo CH, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw YF: Liver biochemical tests and dengue fever. Am J Trop Med Hyg. 1992, 47 (3): 265-270.PubMed Kuo CH, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw YF: Liver biochemical tests and dengue fever. Am J Trop Med Hyg. 1992, 47 (3): 265-270.PubMed
13.
go back to reference Nguyen TL, Nguyen T, Tieu NT: The impact of dengue hemorrhagic fever on liver function. Res Virol. 1997, 148: 273-277. 10.1016/S0923-2516(97)88364-1.CrossRefPubMed Nguyen TL, Nguyen T, Tieu NT: The impact of dengue hemorrhagic fever on liver function. Res Virol. 1997, 148: 273-277. 10.1016/S0923-2516(97)88364-1.CrossRefPubMed
14.
go back to reference Huerre MR, Lan NT, Marianneau P, Hue NB, Khun H, Hung NT, Khen NT, Drouet MT, Huong VT, Ha DQ, Buisson Y, Deubel V: Liver histopathology and biological correlates in five cases of fatal dengue fever in Vietnamese children. Virchows Arch. 2001, 438: 107-115.PubMed Huerre MR, Lan NT, Marianneau P, Hue NB, Khun H, Hung NT, Khen NT, Drouet MT, Huong VT, Ha DQ, Buisson Y, Deubel V: Liver histopathology and biological correlates in five cases of fatal dengue fever in Vietnamese children. Virchows Arch. 2001, 438: 107-115.PubMed
15.
go back to reference Nuovo GJ: Histologic distribution of hepatitis A, B, C, D, E and G with the concomitant cytokine response in liver tissues. Diagn Mol Pathol. 1998, 7: 267-275. 10.1097/00019606-199810000-00006.CrossRefPubMed Nuovo GJ: Histologic distribution of hepatitis A, B, C, D, E and G with the concomitant cytokine response in liver tissues. Diagn Mol Pathol. 1998, 7: 267-275. 10.1097/00019606-199810000-00006.CrossRefPubMed
16.
go back to reference Napoli J, Bishop GA, McGuinness PH, Painter DM, McCaughan GW: Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines. Hepatology. 1996, 24: 759-765. 10.1002/hep.510240402.CrossRefPubMed Napoli J, Bishop GA, McGuinness PH, Painter DM, McCaughan GW: Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines. Hepatology. 1996, 24: 759-765. 10.1002/hep.510240402.CrossRefPubMed
17.
go back to reference Seneviratne SL, Malavige GN, de Silva HJ: Pathogenesis of liver involvement during dengueviral infections. Trans R Soc Trop Med Hyg. 2006, 100: 608-614. 10.1016/j.trstmh.2005.10.007.CrossRefPubMed Seneviratne SL, Malavige GN, de Silva HJ: Pathogenesis of liver involvement during dengueviral infections. Trans R Soc Trop Med Hyg. 2006, 100: 608-614. 10.1016/j.trstmh.2005.10.007.CrossRefPubMed
18.
go back to reference Stalin V, Nayyar I, Anemon PP G, Shyam K: Fatal fulminant hepatic failure in a diabetic with primary dengue. J Trop Med. 2010, 2010: 413561- Stalin V, Nayyar I, Anemon PP G, Shyam K: Fatal fulminant hepatic failure in a diabetic with primary dengue. J Trop Med. 2010, 2010: 413561-
19.
go back to reference Chaturvedi UC, Agarwal R, Elbishbishi EA, Mustafa AS: Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis. FEMS Immunol Med Microbiol. 2000, 28 (3): 183-188. 10.1111/j.1574-695X.2000.tb01474.x.CrossRefPubMed Chaturvedi UC, Agarwal R, Elbishbishi EA, Mustafa AS: Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis. FEMS Immunol Med Microbiol. 2000, 28 (3): 183-188. 10.1111/j.1574-695X.2000.tb01474.x.CrossRefPubMed
20.
go back to reference Khongphatthanayothin A, Lertsapcharoen P, Supachokchaiwattana P, Satupan P, Thongchaiprasit K, Poovorawan Y: Hepatosplanchnic circulatory dysfunction in acute hepatic infection: the case of dengue hemorrhagic fever. Shock. 2005, 24 (5): 407-411. 10.1097/01.shk.0000180981.70870.8c.CrossRefPubMed Khongphatthanayothin A, Lertsapcharoen P, Supachokchaiwattana P, Satupan P, Thongchaiprasit K, Poovorawan Y: Hepatosplanchnic circulatory dysfunction in acute hepatic infection: the case of dengue hemorrhagic fever. Shock. 2005, 24 (5): 407-411. 10.1097/01.shk.0000180981.70870.8c.CrossRefPubMed
21.
go back to reference Khongphatthanayathin A, Mahayosnond A, Yong P: Possible cause of liver failure in patient with dengue shock syndrome. Emerg Infect Dis J. 2013, 19 (7): 1161-1163. 10.3201/eid1907.121820.CrossRef Khongphatthanayathin A, Mahayosnond A, Yong P: Possible cause of liver failure in patient with dengue shock syndrome. Emerg Infect Dis J. 2013, 19 (7): 1161-1163. 10.3201/eid1907.121820.CrossRef
22.
go back to reference Sirisena PDNN, Noordeen F: Evolution of dengue in Sri Lanka-changes in virus, vector and climate. Int J Infect Dis. 2014, 19: 6-12.CrossRefPubMed Sirisena PDNN, Noordeen F: Evolution of dengue in Sri Lanka-changes in virus, vector and climate. Int J Infect Dis. 2014, 19: 6-12.CrossRefPubMed
23.
go back to reference Fabre A, Couvelard A, Degott C, Lagorce-Pages C, Bruneel F, Bouvet E, Vachon F: Dengue virus induced hepatitis with chronic calcific changes. Gut. 2001, 49 (6): 864-865. 10.1136/gut.49.6.864.CrossRefPubMedPubMedCentral Fabre A, Couvelard A, Degott C, Lagorce-Pages C, Bruneel F, Bouvet E, Vachon F: Dengue virus induced hepatitis with chronic calcific changes. Gut. 2001, 49 (6): 864-865. 10.1136/gut.49.6.864.CrossRefPubMedPubMedCentral
24.
go back to reference Mourao MP, Lacerda MV, Bastos Mde S, Albuquerque BC, Alecrim WD: Dengue hemorrhagic fever and acute hepatitis: a case report. Braz J Infect Dis. 2004, 8 (6): 461-464. 10.1590/S1413-86702004000600011.CrossRefPubMed Mourao MP, Lacerda MV, Bastos Mde S, Albuquerque BC, Alecrim WD: Dengue hemorrhagic fever and acute hepatitis: a case report. Braz J Infect Dis. 2004, 8 (6): 461-464. 10.1590/S1413-86702004000600011.CrossRefPubMed
25.
go back to reference Rosen L, Khin MM UT: Recovery of virus from the liver of children with fatal dengue: reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever. Res Virol. 1989, 140 (4): 351-360.CrossRefPubMed Rosen L, Khin MM UT: Recovery of virus from the liver of children with fatal dengue: reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever. Res Virol. 1989, 140 (4): 351-360.CrossRefPubMed
26.
go back to reference Morier L, Kouri G, Guzman G, Soler M: Antibody-dependent enhancement of dengue 2 virus in people of white descent in Cuba. Lancet. 1987, 1 (8540): 1028-1029.CrossRefPubMed Morier L, Kouri G, Guzman G, Soler M: Antibody-dependent enhancement of dengue 2 virus in people of white descent in Cuba. Lancet. 1987, 1 (8540): 1028-1029.CrossRefPubMed
27.
28.
go back to reference Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV: Dengue and dengue haemorrhagic fever. Lancet. 1998, 352 (9132): 971-977. 10.1016/S0140-6736(97)12483-7.CrossRefPubMed Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV: Dengue and dengue haemorrhagic fever. Lancet. 1998, 352 (9132): 971-977. 10.1016/S0140-6736(97)12483-7.CrossRefPubMed
29.
go back to reference Poovorawan Y, Hutagalung Y, Chongsrisawat V, Boudville I, Bock HL: Dengue virus infection: a major cause of acute hepatic failure in Thai children. Ann Trop Paediatr. 2006, 26 (1): 17-23. 10.1179/146532806X90565.CrossRefPubMed Poovorawan Y, Hutagalung Y, Chongsrisawat V, Boudville I, Bock HL: Dengue virus infection: a major cause of acute hepatic failure in Thai children. Ann Trop Paediatr. 2006, 26 (1): 17-23. 10.1179/146532806X90565.CrossRefPubMed
30.
go back to reference Kumarasena RS, Senanayake M, Sivaraman K, de Silva A, Dassanayake AS, Premaratna R, Wijesiriwardena B, de Silva HJ: Intravenous N-acetylcysteine in dengue-associated acute liver failure. Hepatol Int. 2010, 4 (2): 533-534. 10.1007/s12072-010-9176-4.CrossRefPubMedPubMedCentral Kumarasena RS, Senanayake M, Sivaraman K, de Silva A, Dassanayake AS, Premaratna R, Wijesiriwardena B, de Silva HJ: Intravenous N-acetylcysteine in dengue-associated acute liver failure. Hepatol Int. 2010, 4 (2): 533-534. 10.1007/s12072-010-9176-4.CrossRefPubMedPubMedCentral
Metadata
Title
Extensive haemorrhagic necrosis of liver is an unpredictable fatal complication in dengue infection: a postmortem study
Authors
SAM Kularatne
IVB Imbulpitiya
RA Abeysekera
RN Waduge
RPVJ Rajapakse
KGAD Weerakoon
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-141

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