Intravenous N-Acetylcysteine in Patients With Dengue Fever With Marked Aminotransferase Elevation: Prospective Comparative Study

Background Dengue fever can lead to significant hepatic involvement and marked aminotransferase elevation and is associated with increased morbidity and prolonged hospitalization. N-acetylcysteine (NAC) has been proposed as a supportive therapy for dengue-induced liver injury. However, prospective comparative evidence from endemic regions such as Vietnam remains limited. Objective This study aimed to evaluate the association between intravenous NAC administration and clinical outcomes (primarily length of hospital stay), as well as the secondary effects of NAC on liver transaminase levels (posttreatment aspartate aminotransferase [AST] and alanine aminotransferase [ALT] and their changes from baseline) and platelet recovery in patients with dengue fever with marked aminotransferase elevation (AST or ALT ≥400 U/L). Methods A prospective, nonrandomized comparative study was conducted at the Department of Tropical Diseases, Viet Tiep Hospital, Hai Phong, Vietnam, from June to December 2024. A total of 128 adult patients with laboratory-confirmed dengue fever and marked aminotransferase elevation (AST and/or ALT ≥400 U/L) were enrolled. Treatment allocation was not randomized and was determined by the treating physicians based on aminotransferase elevation and overall clinical condition. Patients received either intravenous NAC (100 mg per kilogram per day) plus standard supportive care (NAC group; n=68) or standard care alone (non-NAC group; n=60). The primary outcome was length of hospital stay. Secondary outcomes included liver transaminase levels and platelet recovery at discharge. Results Baseline AST, ALT, bilirubin, and international normalized ratio values were broadly comparable between groups, although several clinical and hematological characteristics differed at baseline. The NAC group had a significantly shorter hospital stay (mean 5.01, SD 1.28 vs 6.12, SD 1.25 days; P<.001). The AST and ALT levels were significantly lower in the NAC group (AST: mean 154.83, SD 67.22 vs 184.62, SD 79.88 U/L and P=.02; ALT: mean 113.09, SD 33.31 vs 156.35, SD 73.66 U/L and P=.004). The posttreatment platelet count was significantly higher in the NAC group (median 31.50, IQR 19.00-50.15 G/L vs 17.00, IQR 8.75-36.23 G/L; P=.001). The median increase in platelet count was also greater in the NAC group (15.05, IQR 7.05-26.10 G/L vs 6.95, IQR 4.22-15.43 G/L; P=.001). No severe infusion-related adverse events were documented during the study period. Conclusions In this prospective, nonrandomized comparative study, intravenous NAC administration was associated with shorter hospitalization and lower posttreatment aminotransferase levels in adult patients with dengue fever and marked aminotransferase elevation. No severe infusion-related adverse events were documented during the study period. However, the nonrandomized design and potential for confounding limit causal inference. Larger, multicenter randomized controlled trials are warranted to clarify the therapeutic role of NAC in dengue-related hepatic complications.