N-Acetylcysteine in the Management of Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis (SBP) is one of the most serious infectiouscomplications of liver cirrhosis and ascites. It affects approximately 10‐30% ofhospitalized patients with decompensated cirrhosis and carries an in‐hospital mortalityof 20‐40% despite appropriate antimicrobial therapy. SBP results from bacterialtranslocation across the intestinal mucosa together with cirrhosis‐associated immunedysfunction, leading to impaired bacterial clearance and exaggerated systemicinflammation. Current international guidelines recommend immediate empirical antibiotictherapy together with intravenous human albumin to reduce the incidence of acute kidneyinjury (AKI), hepatorenal syndrome, and mortality.Although this strategy has substantially improved outcomes, treatment failure, persistentinfection, renal dysfunction, acute‐on‐chronic liver failure (ACLF), and early mortalityremain common, indicating that currently available therapy does not adequately addressall pathogenic mechanisms of SBP. Increasing evidence suggests that oxidative stress is acentral contributor to the progression of bacterial infections in cirrhosis. Excessiveproduction of reactive oxygen species aggravates hepatocellular injury, endothelialdysfunction, immune dysregulation, and renal impairment, thereby amplifying systemicinflammatory responses during SBP. Consequently, therapeutic strategies targetingoxidative stress may improve host defense while limiting organ injury.N‐acetylcysteine (NAC) is a precursor of glutathione and one of the most extensivelystudied antioxidant agents in clinical medicine. Besides restoring intracellularglutathione stores, NAC exerts anti‐inflammatory, endothelial‐protective, andimmunomodulatory effects through inhibition of oxidative stress and pro‐inflammatorycytokine production. On the other hand, experimental studies have further demonstratedthat NAC can inhibit bacterial biofilm formation, enhance antibiotic penetration, andpotentiate antimicrobial activity against several clinically important bacterialpathogens.Despite these promising biological properties, the therapeutic role of NAC in active SBPhas not been established. Previous data have primarily evaluated NAC for hepato‐ or renalprotection in liver disease. While its potential role as an adjunctive antibacterialtherapy during active SBP has not been investigated in adequately designed randomizedcontrolled trials. Therefore, the present study will evaluate whether adjunctive NACimproves early treatment response and reduces subsequent organ dysfunction and short‐termadverse outcomes.