Intravenous N-acetylcysteine in dengue-associated acute liver failure

Abstract

We read with interest the article by Mumtaz et al. [1] on the role of oral N-acetylcysteine (NAC) in adults with nonacetaminophen-induced acute liver failure. We agree that their findings are of particular relevance to many developing countries, where liver transplantation is neither available nor affordable. There has been another recent study in which intravenous NAC has been shown to improve transplant-free survival in early-stage non-acetaminophen-induced acute liver failure in adults [2]. We report our initial experience in treating acute liver failure caused by dengue infection with NAC. Use of NAC in this situation has not been previously described.Sri Lanka is experiencing its worst-ever dengue epidemic yet, with more than 250,000 reported cases and more than 250 deaths, mainly adults, since January 2009. Severe hepatic and cardiac complications and a higher than usual mortality have been notable features of this epidemic. Mild-moderate elevations in serum aminotransferase levels are very common in dengue, but acute liver failure can also occur [3] and has a poor outcome, with case fatality rates of up to 50% in children [4]. There is little information on the management of dengue-associated acute liver failure. There are isolated reports of rapid improvement in the biochemical profile and encephalopathy with molecular adsorbent recirculating system [5]. Liver transplantation is difficult because of hemodynamic instability, bleeding manifestations, and organ dysfunction caused by the infection itself, and may not be a treatment option in most countries where dengue is prevalent.We retrospectively analyzed the outcome of eight consecutive adult patients (5 men and 3 women; age range, 28-64 years) presenting during the current epidemic with serologically confirmed dengue-associated acute liver failure. In addition to other supportive management [6,7], they received NAC 150 mg/kg loading dose by intravenous administration over 15 min followed by 12.5 mg/kg/h for 4 h and then 6.25 mg/kg/h for up to 72 h. Two patients had dengue hemorrhagic fever [6], six had dengue shock syndrome [6], seven had pleural effusions, and five had ascites. Five patients had early-stage pretreatment hepatic encephalopathy (coma grades I-II), and three had advanced encephalopathy (coma grades III-IV). Time from disease onset to appearance of encephalopathy was 5-8 days. Worst recorded pretreatment value ranges for the eight patients were as follows: platelet count = 6,000-30,000/mm 3 ; international normalized ratio = 1.6-3.2; serum bilirubin = 2.7-12.2 mg/dL; alanine aminotransferase = 4,070-19,800 IU/L; aspartate aminotransferase = 4,455-26,500 IU/L; serum albumin = 2.7-3.9 g/dL; serum globulin = 3.1-3.9 g/dL; and serum creatinine = 0.7-2.5 mg/dL. None had taken acetaminophen more than the prescribed therapeutic dose, used hepatotoxic drugs, or had a history of alcohol abuse. Serology was negative for hepatitis A, B, C, and E, leptospira, and rickettsiae. All patients underwent computerized tomography of the brain to exclude intr...

Predicting acute liver failure in dengue infection

“…Intravenous NAC improves transplant-free survival in early stage non-acetaminophen acute liver failure. Several case reports and case series suggest early use of NAC many improve survival in dengue associated ALF [4]. Early prediction and recognition of ALF in DI may, therefore, be helpful to identify patients who may benefit from treatment with intravenous NAC.…”

“…Although the true incidence is not known, dengue associated ALF is not uncommon and has a poor prognosis [2,3]. Early identification of impending ALF in DI will help clinicians to identify patients who will benefit from interventions such as intravenous N-acetyl cysteine (NAC) [4]. The objective of this study was to identify early clinical and biochemical predictors of ALF in DI.…”

Successful use of intravenous N-acetylcysteine in dengue haemorrhagic fever with acute liver failure

“…There are a few studies with successful use of Nacetylcysteine in non-acetaminophen induced acute liver failure including dengue fever [7,8,9]. NAC may benefit patients with nonacetaminophen induced acute liver failure by improving systemic haemodynamics, by tissue oxygen delivery or via other favourable effects on the acutely injured liver.…”

“…NAC may benefit patients with nonacetaminophen induced acute liver failure by improving systemic haemodynamics, by tissue oxygen delivery or via other favourable effects on the acutely injured liver. The benefit is seen when NAC is used in the early stages of liver failure but not when it is advanced [8,9] . This patient presented with dengue haemorrhagic fever with acute liver failure and grade 2 hepatic encephalopathy.…”

Pathogenesis of severe dengue infection

“…In addition, organ failure should be treated on its own merits. There are ongoing efforts to develop specific antiviral drugs and other treatment modalities that may improve the outcome of dengue infection [37] and its associated organ specific complications, such as, the use of N-acetylcysteine in ALF [38,39]. More research, including randomised clinical trials, is required to replace much of the dogma with evidence based management practices.…”