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.

The role of transjugular intrahepatic portosystemic shunt in patients with cirrhosis and ascites: Recent evolution and open questions

“…Cure/removal of etiological factor(s) responsible for chronic liver disease has a major positive impact on the natural history of cirrhosis. [76] In fact, etiological cure/removal may not only reduce disease progression but also reverse the disease from decompensation to recompensation. [77] Theoretically, by achieving recompensation without placing a TIPS, one would also prevent potential shunt-related complications.…”

Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions

“…In the light of the recent evidence regarding the unexpectedly beneficial effects of statins in cirrhosis, their use in cirrhotic patients has evolved from being risky to possibly promising [ 33 ]. As a result, many studies have been designed to further characterize such theoretically favorable effects in the primary and secondary prevention of cirrhosis [ 34 , 35 ].…”

Toward a more precise prognostic stratification in acute decompensation of cirrhosis: The Padua model 2.0

“…6,7 However, better identification of patients with AD at higher risk of progression would improve patient management (i.e., identification of candidates for an expedite evaluation for liver transplantation and/or disease-modifying therapies currently under investigation). [8][9][10] The cluster of differentiation 14 (CD14) is a glycoprotein expressed on the external membrane of monocytes and macrophages (i.e., innate immune system cells). 11 CD14 is a pattern recognition molecule that activates a proinflammatory signaling pathway responsible for the innate response to pathogens upon recognition of the complexes between lipopolysaccharide (LPS) and LPS-binding proteins.…”

“…Although our understanding of the pathophysiology of AD‐ACLF syndrome has improved in the recent years, 4 leading to the “systemic inflammation hypothesis,” 5 prediction of the individual patient's trajectory after AD remains challenging 6,7 . However, better identification of patients with AD at higher risk of progression would improve patient management (i.e., identification of candidates for an expedite evaluation for liver transplantation and/or disease‐modifying therapies currently under investigation) 8–10 …”