ÇOCUKLARDA PARASETAMOL ZEHİRLENMESİ DIŞINDA AKUT KARACİĞER HASARINDA N-ASETİL SİSTEİN KULLANIMI

Abstract

Gurbetoğlu Ö., Use of N-Acetylcysteine in Acute Liver Injury Other Than Paracetamol Poisoning in Children. Hacettepe University Faculty of Medicine Department of Pediatrics, Residency Thesis, Ankara, 2026. Available data regarding the effects of N-acetylcysteine (NAC) therapy on the clinical and biochemical course of pediatric acute liver failure (ALF) are limited and heterogeneous. The present study aimed to longitudinally evaluate response dynamics to NAC therapy, as well as the impact of cholestasis and the underlying mechanism of liver injury on prognosis in non-paracetamol pediatric ALF. In this single-center retrospective cohort study, 86 pediatric patients with ALF followed at a tertiary referral center were included. Patients were stratified according to the presence of cholestasis, response to NAC therapy, and the mechanism of liver injury. Longitudinal changes in model end stage liver disease (MELD) and pediatric end stage liver disease (PELD) scores, INR, ALT, direct bilirubin, lactate, and phosphate levels were analyzed using linear mixed models. Multiorgan failure, need for extracorporeal therapies, and survival outcomes were also assessed. The mean age of the patients was 6.68 ± 5.96 years, with a median age of 4.35 years (IQR: 1.74–11.30). A total of 39.5% of patients clustered within the 1–5.5-year age range. Secondary liver injury accounted for 40.7% of cases. At least one chronic disease or comorbidity was present in 38.4% of patients, with cardiac diseases being the most common (22.1%). Viral etiologies were detected in 20.9% of cases by respiratory panels and in 18.6% by serological tests. At least one extrahepatic organ failure was observed in 75.6% of patients, with 44.2% experiencing two or more organ failures. During follow-up, 53.5% needed inotropic support, 38.4% required mechanical ventilation, and 50.0% received broad-spectrum antibiotics. Renal failure was present in 32.6% of cases, and 57% of these patients needed continuous renal replacement therapy (CRRT). Overall, 39.5% of patients (n=34) received at least one extracorporeal treatment. The most used was therapeutic plasma exchange (TPE) (33.7%), followed by CRRT (18.6%), hemodialysis (8.1%), and extracorporeal membrane oxygenation (ECMO) (5.8%). Among TPE patients, the mean number of sessions was 6, with a median of 3. One, two, and three modalities were used in 18.6%, 12.8%, and 8.1% of patients, respectively. Data on hepatic encephalopathy (HE) grading were available for 23.3% of patients (n = 20), of whom 52.7% were classified as having advanced HE (grades 3–4). Overall mortality rate was 24.4% (n = 21), with non-survivors having a median age of 2.3 years. Among non-survivors, 85.7% experienced extrahepatic organ failure, and 38% having four organ system failures. Renal failure occurred in 47.6%, inotropic support was administered to 81%, and 57% required mechanical ventilation. In linear mixed models, cholestasis was associated with a significant increase in MELD/PELD score (+8.61 points; p<0.001), whereas time had a significant main effect on trajectories of INR, ALT, and bilirubin (p<0.001 for all). NAC therapy was associated with improved spontaneous survival in patients with toxic hepatitis and secondary liver injury, warranting further prospective evaluation. Models demonstrated high overall explanatory power for the combined fixed and random effects, indicating that interindividual heterogeneity substantially influenced the clinical course. These findings support the adoption of longitudinal, comprehensive, and etiology-driven monitoring strategies rather than static assessment approaches in the management of pediatric ALF, and underscore the need for further prospective, controlled studies to more clearly define the role of NAC therapy in this population.