Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents

Abstract

The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, even when etiological treatment has been effective, a significant proportion of patients with decompensated cirrhosis remains at risk of further disease progression. Therefore, therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis could represent a new approach for the management of these severely ill patients. Some of the interventions currently employed for treating or preventing specific complications of cirrhosis or used in other diseases (i.e., poorly absorbable oral antibiotics, statins, albumin) have been proposed as potential disease-modifying agents in cirrhosis (DMAC) since clinical studies have shown their capacity of improving survival. Additional multicenter, large randomized clinical trials are awaited to confirm these promising results. Finally, new drugs able to antagonize key pathophysiological mechanisms are under pre-clinical development or at the initial stages of clinical assessment.

Keywords: TIPS; ascites; decompensated cirrhosis; human albumin; non-selective beta-blockers; portal hypertension; rifaximin; statins.

Figure 1

Targets of action of available treatments antagonizing key pathophysiological events in decompensated cirrhosis. See text for details. TIPS: trans-jugular intra-hepatic porto-systemic shunt; STAT: statins; NSBB: non-selective beta-blockers; G-CSF: granulocyte colony stimulating factors; PAA: poorly absorbable antibiotics.