• alanine transaminase
• aspartate aminotranferase
• dengue
• liver failure
• severe dengue

• Humans
• Dengue/diagnosis
• Dengue/complications
• Dengue/pathology
• Dengue/virology
• Dengue Virus
• Liver/pathology
• Liver/virology
• Liver/diagnostic imaging
• Liver Diseases/virology
• Liver Diseases/etiology
• Liver Diseases/pathology
• Liver Diseases/diagnosis

• La Martinique Hospital
• Institut Pasteur in New Caledonia

• Acute liver failure
• Cholestasis
• Cytosorb®
• Dengue fever
• Dengue haemorrhagic fever
• Therapeutic plasma exchange

• Acute liver failure
• Cytokine storm
• Dengue hemorrhagic fever
• Dengue viral infection
• Hepatocyte apoptosis
• Liver injury
• Liver involvement
• Severe dengue disease

• Dengue
• Lactate
• Liver failure
• MELD
• Predictors
• Transaminase

Dengue is a common arboviral infection with a diverse spectrum of clinical manifestations. Dengue hemorrhagic fever is a more severe form of infection characterized by plasma leak and hemoconcentration. Although hepatic dysfunction is common in dengue illness, massive liver necrosis is rarely reported. Lactic acidosis is a poor prognostic marker in liver failure related to dengue. Management of acute renal injury in dengue hemorrhagic fever due to prolonged shock is challenging as the fluid reabsorption during the recovery phase expands the intravascular volume and precipitates heart failure and pulmonary edema.

We report the case of a 43-year-old Sri Lankan Sinhalese woman with serologically confirmed dengue fever presenting with evidence of plasma leakage developing acute liver failure evidenced by deranged liver functions, coagulopathy, and altered sensorium and acute kidney injury with anuria. She had elevated serum lactate levels. In addition to the “standard care,” she was managed with intravenously administered N-acetyl cysteine and blood transfusions, even in the absence of bleeding or dropping packed cell volume, targeting a higher packed cell volume anticipating a better oxygenation at tissue level. Continuous veno-venous hemodialysis was employed and continued for 138 hours removing the fluids reabsorbed during the recovery phase to prevent her from developing heart failure and pulmonary edema. She made full recovery with no sequelae.

N-acetyl cysteine and packed cell transfusion aiming at a higher packed cell volume to maintain adequate tissue perfusion during shock may be beneficial in acute liver failure due to dengue virus. The use of a continuous form of renal replacement such as continuous veno-venous hemodialysis is of paramount importance in managing fluid states in the recovery phase of dengue hemorrhagic fever in those with renal impairment. Interesting observations made in the fluid dynamics during the reabsorption phase need further studies preferably with an animal model.

• Acute kidney injury
• Continuous veno-venous hemodialysis (CVVHD)
• Dengue hemorrhagic fever
• Liver failure
• N-acetyl cysteine
• Packed cell transfusion

Dengue virus (DENV) is the most prevalent mosquito-borne viral illness in humans. Currently, there are no therapeutic agents available to prevent or treat DENV infections. Our objective was to fill this unmet medical need by evaluating the antiviral activity of interferon-α (IFN) and ribavirin (RBV) as a combination therapy against DENV. DENV-infected Vero and Huh-7 cells were exposed to RBV and/or IFN, and the viral burden was quantified over time by plaque assay. Drug-drug interactions for antiviral effect were determined by fitting a mathematical model to the data. We then assessed clinically-relevant exposures of IFN plus RBV using the hollow fiber infection model (HFIM) system. RBV monotherapy was only effective against DENV at toxic concentrations in Vero and Huh-7 cells. IFN, as a single agent, did inhibit DENV replication at physiological concentrations and viral suppression was substantial in Huh-7 cells (Half maximal effective concentration (EC₅₀) = 58.34 IU/mL). As a combination therapy, RBV plus IFN was additive for viral suppression in both cell lines; however, enhancement of antiviral activity at clinically-achievable concentrations was observed only in Huh-7 cells. Finally, clinical exposures of RBV plus IFN suppressed DENV replication by 99% even when treatment was initiated 24 h post-infection in the HFIM. Further evaluation revealed that the antiviral effectiveness of the combination regimen against DENV is mostly attributed to activity associated with IFN. These findings suggest that IFN is a potential therapeutic strategy for the treatment of DENV.

• Dengue virus
• antiviral therapy
• combination therapy
• hollow fiber infection model
• interferon-α
• mathematical modeling
• ribavirin

Dengue is a common arboviral infection with a clinically diverse spectrum of presentations. Although hepatic dysfunction is commonly identified in patients will dengue illness, acute liver failure is rare. The etiopathogenesis of hepatic dysfunction is multifactorial and related to direct viral invasion of hepatocytes, immunological factors and hypoxia particularly in cases of shock in dengue hemorrhagic fever. Ideal management of dengue-related hepatic dysfunction and acute liver failure is still debated.

We report a 53-year-old Sri Lankan Sinhalese male with serologically confirmed dengue fever presenting with evidence of plasma leakage developing acute liver failure evidenced by deranged liver functions, coagulopathy and altered sensorium. In addition to the ‘standard care’, the patient was managed with intravenous N-acetyl cysteine and blood transfusions even in the absence of bleeding or dropping packed cell volume (PCV), targeting a higher PCV in anticipation of better oxygenation at tissue level. He made a full recovery with no sequential infections.

N-acetyl cysteine and packed cell transfusion aiming at a higher PCV to maintain adequate tissue perfusion during shock may be beneficial in acute liver failure due to dengue virus. Large randomized trials should be carried out to establish the efficacy of these treatment strategies to support these observations and change the current practice.

• Dengue hemorrhagic fever
• Hepatitis
• Liver
• N-acetyl cysteine
• Packed cell transfusion

• acetaminophen
• alcohol consumption
• dengue infection
• natural killer cell
• transaminitis

• Hepatitis
• Injury
• Liver
• Shock

• ACLF, acute-on-chronic liver failure
• ALF, acute liver failure
• CMV, cytomegalovirus
• DHF, dengue hemorrhagic fever
• EEG, electroencephalogram
• HIV, human immunodeficiency virus
• HLH, hemophagocytic lymphohistiocytosis
• MSOF, multisystem organ failure
• SAHF, subacute hepatic failure
• acute liver failure
• dengue fever
• encephalopathy
• jaundice
• malaria

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.

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

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.

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.