Welcome to Module 1

This module is introduced by Paolo Angeli, Full Professor of Internal Medicine at the University of Padova, Italy, together with Marta Tonon, Consultant Physician at the Unit of Internal Medicine and Hepatology, University Hospital of Padova.

They will guide you through the natural history of cirrhosis, with a particular focus on the transition from compensated to decompensated disease and its profound clinical and prognostic implications. Understanding when, how, and why cirrhosis decompensates is a cornerstone of modern hepatology and a prerequisite for effective clinical decision-making in advanced liver disease.

Cirrhosis has traditionally been classified into compensated and decompensated phases, each associated with distinct clinical courses and markedly different survival rates. The onset of decompensation represents a critical turning point in the disease trajectory, as it is associated with a substantial worsening of prognosis and constitutes the most important stratification factor for the risk of death.

In this module, particular attention is given to acute decompensation, defined as the sudden development of ascites, gastrointestinal bleeding, hepatic encephalopathy, infection, or a combination of these events requiring hospitalization. You will explore the two major pathophysiological drivers of acute decompensation—systemic inflammation and portal hypertension—and how their interaction shapes clinical presentation and outcomes.

Acute decompensation is a heterogeneous condition with distinct clinical courses, ranging from pre–acute-on-chronic liver failure (pre-ACLF), characterized by high short- and mid-term mortality, to unstable decompensated cirrhosis with intermediate risk, and stable decompensated cirrhosis, which does not progress to ACLF and is associated with a relatively low 1-year mortality. In parallel, the module addresses non-acute decompensation, a clinically and pathophysiologically distinct entity marked by a gradual worsening of symptoms such as ascites, mild hepatic encephalopathy, and non-obstructive jaundice.

Through a series of focused lectures, this module will provide a clear conceptual framework to understand the patterns and trajectories of decompensated cirrhosis, helping you interpret disease evolution over time and anticipate clinical outcomes.

Upon completing Module 1, students will be able to:

• Distinguish between compensated and decompensated cirrhosis and recognize their differing clinical courses and outcomes
• Identify the various forms of decompensated cirrhosis, including acute and non-acute presentations
• Understand the mechanisms and patterns underlying the development of decompensation
• Recognize the different clinical trajectories following decompensation and their prognostic implications