Abstract
This systematic review evaluates the effectiveness of non-selective beta-blockers (NSBBs) in preventing first decompensation and disease progression in patients with compensated cirrhosis, with emphasis on those with clinically significant portal hypertension (CSPH). Six randomized controlled trials (RCTs) were analyzed, representing both historic endoscopy-based studies and modern hemodynamically defined cohorts. The synthesis demonstrates that NSBBs confer meaningful benefit only after the hemodynamic threshold of CSPH is reached, as exemplified by contemporary trials showing reduced risk of decompensation, particularly ascites, while earlier studies enrolling patients without confirmed CSPH or with mild portal hypertension did not demonstrate benefit and, in some cases, suggested potential harm. Carvedilol showed additional promise in delaying variceal progression even with modest HVPG reduction, indicating potential mechanisms beyond portal pressure lowering. Across trials, the variability in outcomes was explained by differences in baseline hemodynamic severity, selection criteria, and methodological rigor, highlighting the importance of disease-stage-specific application. Overall, the findings support a shift toward targeted NSBB therapy in compensated cirrhosis with confirmed or probable CSPH, rather than universal prophylaxis in all compensated patients.