Preventing First and Further Decompensation in Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) remains a major cause of global morbidity and mortality. Preventing hepatic decompensation-both the first event and subsequent recurrences-has become a central therapeutic goal to prolong survival. The transition from the compensated phase (cACLD) to the decompensated phase (dACLD) is driven by clinically significant portal hypertension (CSPH) and continuous exposure to etiologic factors, and is often precipitated by systemic triggers such as infections, portal vein thrombosis, and hepatocellular carcinoma. Thus, effective prevention requires a multidisciplinary strategy combining etiologic control with hemodynamic modulation, supported by vaccination, optimized nutrition and physical activity, judicious endoscopic therapy, and a critical reassessment of antibiotic prophylaxis in the era of antimicrobial resistance. Among non-selective beta-blockers (NSBBs), carvedilol-through combined β1/β2 and α1 blockade-achieves a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol and demonstrates superiority in preventing first decompensation. In dACLD, although the effect of NSBBs is attenuated, carvedilol still emerges as the preferred option, given that propranolol shows significantly lower efficacy at this stage. Endoscopic variceal ligation (EVL) remains an alternative for NSBB-intolerant patients in cACLD and is essential for secondary prophylaxis. Moreover, in dACLD, the combination of EVL with carvedilol is increasingly being explored in Child-Pugh B/C patients. We provide an overview of pathophysiological mechanisms, risk stratification using non-invasive tests, and pragmatic prevention strategies across the different stages of disease, emphasizing recompensation, the NSBB "therapeutic window," and the need to revisit routine antibiotic prophylaxis.