Liver cirrhosis poses major challenges for both individual health and global healthcare systems. Recent studies have challenged the traditional and predictable linear course of cirrhosis, demonstrating marked heterogeneity in the patterns of the first decompensating events. This review presents an updated epidemiology of cirrhosis and its main causes, outlines an overview of the clinical features, and explores the evolving concepts of the spectrum of decompensation. It further delineates recent advancements in the diagnosis, prognostic scoring, and management of decompensated cirrhosis and the subsequent clinically challenging complications of portal hypertension. Emerging innovations in non-invasive imaging, diagnostic serum biomarkers, and etiology-specific therapies, together with the development of novel liver support systems, underscore a paradigm shift toward a multimodal approach for cirrhosis care. Furthermore, the integration of precision medicine into clinical practice holds promise for reshaping the future of liver cirrhosis management in the coming decades.

Introduction: The recently developed Freiburg Index of Post‐TIPS Survival (FIPS) allows improved risk classification of patients with decompensated cirrhosis allocated to transjugular intrahepatic portosystemic shunt (TIPS) implantation. This study investigated the prognostic value of the FIPS in patients hospitalized with acute decompensation of cirrhosis (AD), outside the setting of TIPS implantation.Methods: A total of 1133 patients with AD were included in a retrospective, multi‐centre study. Ninety‐day, 180‐day and 1‐year mortality were recorded and the FIPS' performance in predicting mortality at these time points was analysed using ROC analyses.Results: Ninety‐day, 180‐day and 1‐year mortality were 17.7%, 24.4% and 30.8%. Uni‐ and multivariable Cox regression models showed that the FIPS independently predicted 1‐year mortality in the study cohort (HR 1.806, 95% CI 1.632–1.998, p < .0001). In ROC analyses, the FIPS offered consistently high performance in the prediction of mortality within 1 year after AD (area under the receiver operator characteristic [AUROC]: 1‐year mortality .712 [.679–.746], 180‐day mortality .740 [.705–.775] and 90‐day mortality .761 [.721–.801]). In fact, in the subgroup of patients presenting with variceal bleeding, the FIPS even showed significantly improved discriminatory performance in the prediction of long‐term mortality (AUROC 1‐year mortality: .782 [.724–.839]) in comparison with established prognostic scores, such as the CLIF‐C AD score (.724 [.660–.788], p = .0071) or MELD 3.0 (.726 [.662–.790], p = .0042).Conclusions: The FIPS accurately predicts mortality in patients with AD and seems to offer superior prognostication of long‐term mortality in patients with variceal bleeding.

The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long‐term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis‐related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis‐related complications and discuss key challenges for wide application of long‐term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9‐11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long‐term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature.

Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis.

Numerous cell sources are being explored to replenish functional β-cell mass since the proof-of -concept for cell therapy of diabetes was laid down by transplantation of islets. Many of these cell sources have been shown to possess a degree of plasticity permitting differentiation along new lineages into insulin-secreting β-cells. In this review, we explore emerging reprograming pathways that aim to generate bone fide insulin producing cells. We focus on small molecules and key transcriptional regulators that orchestrate phenotypic conversion and maintenance of engineered cells.