The current approaches to the management of patients with decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. The improved knowledge of the pathophysiological background of advanced cirrhosis, represented by a sustained systemic inflammation strictly linked to a circulatory dysfunction, provides a novel paradigm for the management of these patients, with the ambitious target of modifying the course of the disease by preventing the onset of complications and multiorgan failure; these interventions will eventually improve patients’ quality of life, prolong survival and reduce health-care costs. Besides aetiological treatments, these goals could be achieved by persistently antagonizing key pathophysiological events, such as portal hypertension, abnormal bacterial translocation from the gut, liver damage, systemic inflammation, circulatory dysfunction and altered immunological responses. Interestingly, in addition to strategies based on new therapeutic agents, these targets can be tackled by employing drugs that are already used in patients with cirrhosis for different indications or in other clinical settings, including non-absorbable oral antibiotics, non-selective β-blockers, human albumin and statins. The scope of the present Review includes reporting updated information on the treatments that promise to influence the course of advanced cirrhosis and thus act as disease-modifying agents.
The management of decompensated cirrhosis currently addresses the prevention or treatment of specific complications; disease-modifying agents able to modify the course of decompensated cirrhosis still represent an unmet need.
Removing aetiological factors can halt the progression of chronic liver disease, yet a substantial portion of patients with decompensated cirrhosis do not benefit from even successful aetiological treatments.
Portal hypertension, abnormal translocation of bacterial products from the gut (‘upstream’ events) and the consequent systemic inflammation and circulatory dysfunction (‘downstream’ events) represent the main targets for mechanistic approaches.
Transjugular portosystemic shunt and non-selective β-blockers can be seen as upstream treatments, as they lower portal hypertension and might prevent bacterial translocation.
Bacterial translocation can be antagonized by antibiotic-based and non-antibiotic-based interventions, but the former entail the risk of antibiotic resistance, whereas the efficacy of the latter still needs to be demonstrated.
Human albumin and statins, which are able to simultaneously target several downstream pathophysiological mechanisms, represent promising disease-modifying agents, as they have proved their efficacy in prospective randomized trials.
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The authors thank M. Baldassare for figure editing and A. P. Collins for editing the manuscript.
Nature Reviews Gastroenterology and Hepatology thanks J. Abraldes, M. Peck-Radosavljevic and the other anonymous reviewer(s) for their contribution to the peer review of this work.
M.B. has been a scientific consultant for Baxalta, CSL Behring and Grifols and speaker for AbbVie Italia, Baxalta, CSL Behring, Gilead Science, Grifols and Octapharma. P.C. has been a speaker for Baxalta, Grifols, Kedrion and Octapharma. He also participates in advisory boards for Grifols and has been a scientific consultant for Kedrion. He is also the recipient of a research grant from Octapharma.
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Bernardi, M., Caraceni, P. Novel perspectives in the management of decompensated cirrhosis. Nat Rev Gastroenterol Hepatol 15, 753–764 (2018). https://doi.org/10.1038/s41575-018-0045-2
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Nature Communications (2020)
Hepatology International (2020)