In this episode, Marcelo Kugelmas, MD, and Steven Flamm, MD, discuss strategies to prevent clinical decompensation in patients with cirrhosis and clinically significant portal hypertension. They explore the importance of identifying overlapping liver disease etiologies—such as MASLD/metALD and alcohol-related liver disease—and emphasize a thorough diagnostic approach using non-invasive fibrosis staging tools like transient elastography, ELF, FibroSure, and Fib-4. The conversation highlights the role of liver stiffness measurements and platelet count in diagnosing clinically significant portal hypertension, referencing the latest AASLD guidelines and the “Rule of Fives.” The speakers also review the use of carvedilol as a first-line non-selective beta blocker to reduce the risk of variceal bleeding and improve survival—even in the absence of large varices. They offer clinical insights on when endoscopic variceal banding may still be appropriate and how evolving practices are shaping the future of portal hypertension management. This episode is a must-listen for hepatologists, gastroenterologists, and providers managing patients with advanced chronic liver disease.