Clinical Outcomes of Children Diagnosed Dengue-Associated Acute Liver Failure with or without N-Acetylcysteine Treatment: A Retrospective Cohort Study

Abstract

Objectives N-acetylcysteine (NAC) has been shown to prevent hepatic damage and improve microcirculatory blood flow and oxygen delivery to the tissue. Previous studies have proposed the benefit of NAC in dengue-associated acute liver failure (ALF). However, most studies are descriptive and lack comparison between groups. We aimed to compare the ALF resolution rate and mortality rate of those who received and did not receive NAC treatment. Methods A retrospective cohort study was conducted among children aged <15 years who were diagnosed with dengue-associated ALF at a tertiary hospital in Thailand, between January 2002 and July 2019. Demographic and clinical information were collected. Main outcomes were ALF resolution and mortality rate. Results Thirty-three patients were included of which 16 received NAC treatment (48.5%). Mean ages were 8.5 years (SD 3.7) and mean onset of ALF was 6.3 days (SD 1.6) after onset of fever. The grading of hepatic encephalopathy (HE) and organ failure was not significantly different between the two groups. In the NAC group, 13/16 children were prescribed 100 mg/kg/day of NAC until INR <2 without HE or <1.5 with HE. NAC was initiated 1.1 days (SD 0.3) after the ALF diagnosis. The NAC group showed a higher rate of ALF resolution (75% vs. 53% in the non-NAC group, p = 0.34) with a lower mortality rate (31% vs. 53%, p = 0.36). Side effects of NAC were not found. Conclusion NAC may be beneficial in dengue-associated pediatric ALF. Further well-designed randomized control trials should be carried out.

Acute Liver Failure in Dengue: A Common but Overlooked Entity in Pediatric Patients in Tropical Countries

“…Some of the centers have used NAC in adults with variable results but it is not part of our management protocol and its use was sporadic (21,22). We did not find any significant difference in survival with the use of NAC though Sriphongphankul et al (16) from Thailand found it to be beneficial in dengue PALF. There are occasional case reports of liver transplantation in dengue ALF in adults but in our series, we did not do any (23).…”

“…Hence, dengue ALF needs to be considered in the differential diagnosis of any ALF in endemic areas. In adult patients, the onset of ALF has been observed at a median of 7.5 days (5–13 days) after the inception of fever but in a recent pediatric series, it was 6.3 days (15,16). This is the usual time when derangement in liver enzymes peaks (3).…”

Severe dengue infection unmasking drug‐induced liver injury: Successful management with N‐acetylcysteine

“…Despite limited definitive evidence outside of acetaminophen overdose, 21 NAC is postulated to provide cytoprotective benefits in acute liver failure via replenishing glutathione, scavenging free radicals, and bolstering hepatic regeneration 22 . Studies indicate improved survival with NAC in severe dengue with liver failure 22,23 . While evidence remains scarce, ursodeoxycholic acid's (UDCA) role in idiosyncratic DILI deserves exploration based on existing systematic reviews showing favorable biochemical parameters 24 .…”

“… 22 Studies indicate improved survival with NAC in severe dengue with liver failure. 22 , 23 While evidence remains scarce, ursodeoxycholic acid's (UDCA) role in idiosyncratic DILI deserves exploration based on existing systematic reviews showing favorable biochemical parameters. 24 Further high‐quality randomized controlled trials are necessary to determine whether regimens combining NAC and UDCA offer additive hepatoprotective effects.…”

Non‐hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology

“…Hepatic involvement is characterized by numerous clinical manifestations, ranging from asymptomatic elevations in serum transaminases to ALF 23 . Although the pathogenesis of liver injury secondary to dengue virus infection remains unclear, potential mechanisms include apoptosis in hepatocytes and Kupffer cells, immune‐mediated hepatocyte injury, and shock‐induced ischemic hepatitis 24 . Currently, there is no specific treatment for dengue‐associated ALF; affected patients receive supportive care and measures to prevent further complications.…”