Laura Turco1, Guadalupe Garcia-Tsao2, Ilenia Magnani3, Marcello Bianchini1, Martina Costetti1, Cristian Caporali4, Stefano Colopi4, Emilio Simonini4, Nicola De Maria1, Federico Banchelli5, Rosario Rossi3, Erica Villa1, Filippo Schepis6. 1. Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy. 2. Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy; Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA; Section of Digestive Diseases, VA Connecticut Healthcare System, West Haven, CT, USA. 3. Division of Cardiology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy. 4. Division of Radiology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy. 5. Statistics Unit, Department of Clinical, Diagnostic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy. 6. Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy. Electronic address: filippo.schepis@unimore.it.
Abstract
BACKGROUND & AIMS: The main stages of cirrhosis (compensated and decompensated) have been sub-staged based on clinical, endoscopic, and portal pressure (determined by the hepatic venous pressure gradient [HVPG]) features. Vasodilation leading to a hyperdynamic circulatory state is central in the development of a late decompensated stage, with inflammation currently considered a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation (by C-reactive protein [CRP]) among the different sub-stages of cirrhosis and to investigate their interrelationship and prognostic relevance. METHODS: A single center, prospective cohort of patients with cirrhosis undergoing per protocol hepatic and right-heart catheterization and CRP measurement, were classified into recently defined prognostic stages (PS) of compensated (PS1: HVPG ≥6 mmHg but <10 mmHg; PS2: HVPG ≥10 mmHg without gastroesophageal varices; PS3: patients with gastroesophageal varices) and decompensated (PS4: diuretic-responsive ascites; PS5: refractory ascites) disease. Cardiodynamic states based on cardiac index (L/min/m2) were created: relatively hypodynamic (<3.2), normodynamic (3.2-4.2) and hyperdynamic (>4.2). RESULTS: Of 238 patients, 151 were compensated (PS1 = 25; PS2 = 36; PS3 = 90) and 87 were decompensated (PS4 = 48; PS5 = 39). Mean arterial pressure decreased progressively from PS1 to PS5, cardiac index increased progressively from PS1-to-PS4 but decreased in PS5. HVPG, model for end-stage liver disease (MELD), and CRP increased progressively from PS1-to-PS5. Among compensated patients, age, HVPG, relatively hypodynamic/hyperdynamic state and CRP were predictive of decompensation. Among patients with ascites, MELD, relatively hypodynamic/hyperdynamic state, post-capillary pulmonary hypertension, and CRP were independent predictors of death/liver transplant. CONCLUSIONS: Our study demonstrates that, in addition to known parameters, cardiopulmonary hemodynamics and CRP are predictive of relevant outcomes, both in patients with compensated and decompensated cirrhosis. LAY SUMMARY: There are two main stages in cirrhosis, compensated and decompensated, each with a main relevant outcome. In compensated cirrhosis the main relevant outcome is the development of ascites, while in decompensated cirrhosis it is death. Major roles of cardiac dysfunction and systemic inflammation have been hypothesized in the evolution of the disease in decompensated patients. In this study, we have shown that these factors were also involved in the progression from compensated to decompensated stage.
BACKGROUND & AIMS: The main stages of cirrhosis (compensated and decompensated) have been sub-staged based on clinical, endoscopic, and portal pressure (determined by the hepatic venous pressure gradient [HVPG]) features. Vasodilation leading to a hyperdynamic circulatory state is central in the development of a late decompensated stage, with inflammation currently considered a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation (by C-reactive protein [CRP]) among the different sub-stages of cirrhosis and to investigate their interrelationship and prognostic relevance. METHODS: A single center, prospective cohort of patients with cirrhosis undergoing per protocol hepatic and right-heart catheterization and CRP measurement, were classified into recently defined prognostic stages (PS) of compensated (PS1: HVPG ≥6 mmHg but <10 mmHg; PS2: HVPG ≥10 mmHg without gastroesophageal varices; PS3: patients with gastroesophageal varices) and decompensated (PS4: diuretic-responsive ascites; PS5: refractory ascites) disease. Cardiodynamic states based on cardiac index (L/min/m2) were created: relatively hypodynamic (<3.2), normodynamic (3.2-4.2) and hyperdynamic (>4.2). RESULTS: Of 238 patients, 151 were compensated (PS1 = 25; PS2 = 36; PS3 = 90) and 87 were decompensated (PS4 = 48; PS5 = 39). Mean arterial pressure decreased progressively from PS1 to PS5, cardiac index increased progressively from PS1-to-PS4 but decreased in PS5. HVPG, model for end-stage liver disease (MELD), and CRP increased progressively from PS1-to-PS5. Among compensated patients, age, HVPG, relatively hypodynamic/hyperdynamic state and CRP were predictive of decompensation. Among patients with ascites, MELD, relatively hypodynamic/hyperdynamic state, post-capillary pulmonary hypertension, and CRP were independent predictors of death/liver transplant. CONCLUSIONS: Our study demonstrates that, in addition to known parameters, cardiopulmonary hemodynamics and CRP are predictive of relevant outcomes, both in patients with compensated and decompensated cirrhosis. LAY SUMMARY: There are two main stages in cirrhosis, compensated and decompensated, each with a main relevant outcome. In compensated cirrhosis the main relevant outcome is the development of ascites, while in decompensated cirrhosis it is death. Major roles of cardiac dysfunction and systemic inflammation have been hypothesized in the evolution of the disease in decompensated patients. In this study, we have shown that these factors were also involved in the progression from compensated to decompensated stage.