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Abstract 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.

Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy (OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients with cACLD were enrolled between January 2013 and December 2022. Liver stiffness measurements (LSMs), clinicopathological data, and OGD results were collected. A total of 210 patients were included. The median age was 57 years and 65.7% were male. The main aetiology of cACLD was hepatitis C (41.9%), and 91.9% of patients were Child–Pugh A. HRV prevalence was 12.4%. The Baveno VI criteria (B6C) was the only NIT that could safely reduce the need for OGDs across all aetiologies of cACLD, with a negative predictive value of 98.6 and spared OGD in 33.8%. The FIB-4 would have avoided the most OGDs (71%); however, the HRV miss rate was 6%. The results suggest that the B6C is the best performing NIT in our cohort and reliably excludes HRVs in cACLD patients, regardless of aetiology. This study confirms that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD.

Background Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive therapeutic option to treat the sequelae of portal hypertension. It is unclear whether current international recommendations are reflected in current clinical practice across Australia and the extent of variations in care. This study aimed to address this gap in knowledge and benchmark the current landscape of TIPS services in Australia against international guidelines.Methods We designed a 42-item questionnaire according to practice-based recommendations and standards of international guidelines to investigate current landscape of TIPS service across four key domains: (1) service provision, (2) patient selection and indications, (3) best procedure practice, and (4) postoperative care.Results Gastroenterologist/hepatologists from 23 major liver centres (67.6%) across Australia currently performing TIPS completed the questionnaire. Between 2017 and 2020, there were 456 elective TIPS insertions. Units offering TIPS service had a low median number of TIPS insertions (n=7 per annum). More than half of respondents (56.5%) did not have institutional clinical practice protocols. There was marked variation in practices across institutions in terms of TIPS indications and patient selection. Despite variations, the success rate of elective TIPS was high at 91.7% (79–100%), with 86.6% (29–100%) for rescue TIPS. There was significant variation in postoperative follow-up and care.Conclusion Current TIPS practice in Australia varies significantly across institutions. There is a need for a national consensus clinical practice guidelines to improve access and minimise unwarranted variation. A national registry for TIPS could measure, monitor, and report on quality of clinical care and patient outcomes.

Abstract Objective Delivering effective secondary preventive and integrated care has the potential to break the revolving-door phenomenon of frequent readmissions in patients with advanced chronic liver disease. To address this, we launched the Care Coordination of Liver Disease (CCoLD) pilot, a novel nurse-led cirrhosis clinic in Western Sydney. Methods and analysis Following an index presentation to Blacktown or Mount Druitt hospitals (BMDH), patients (n = 89, matched by age, sex, and MELD-NA) were consecutively either followed up by the CCoLD clinical nurse consultant (intervention cohort) or received standard care (control cohort). Controlled evaluation of the impact of the nurse-led clinic was carried out for a 3-month period including readmission rates, survival, and cost effectiveness. Results The inaugural nurse-led clinic led to improvement in patient-level outcomes including a reduction in unplanned liver-related readmissions (2.08% for intervention cohort vs 12.2% for control cohort, p

A growing body of research suggests that evidence-based interventions can tackle high rates of hospital readmissions among patients with decompensated cirrhosis. Care bundles are a prime example of an evidence-based intervention to reduce hospital readmissions through documentation and communication. In this pilot study, a comprehensive baseline audit of electronic medical records of 497 discharges for 175 patients was conducted to assess the current standards of care on discharge from Blacktown Hospital, Australia, and the scope for introducing a care bundle. Our results demonstrated suboptimal discharge communication in a number of areas: Only 54% of decompensated cirrhosis patients had a follow-up appointment pre-scheduled at discharge. Despite alcohol being identified as a key cause of cirrhosis in 60% of patients, a review by alcohol services was conducted on only 24.9% of patients. Moreover, a general lack of focus on patient education and health literacy was identified. In conclusion, our pilot study has highlighted areas for improvement in the standard of care provided to this cohort of patients. Implementation of a standardized care bundle could address the current shortfalls, improve the standard of care and refocus discharge planning to address health literacy and education in patients admitted with a decompensated liver.

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.

Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14 transcription factors (TFs) in reprogramming MAPCs to induced endodermal progenitor cells (iENDO cells), defined as cells that can be long-term expanded and differentiated to both hepatocyte- and endocrine pancreatic-like cells. We demonstrated that 14 TF-iENDO cells can be expanded for at least 20 passages, differentiate spontaneously to hepatocyte-, endocrine pancreatic-, gut tube-like cells as well as endodermal tumor formation when grafted in immunodeficient mice. Furthermore, iENDO cells can be differentiated in vitro into hepatocyte- and endocrine pancreatic-like cells. However, the pluripotency TF OCT4, which is not silenced in iENDO cells, may contribute to the incomplete differentiation to mature cells in vitro and to endodermal tumor formation in vivo. Nevertheless, the studies presented here provide evidence that reprogramming of adult stem cells to an endodermal intermediate progenitor, which can be expanded and differentiate to multiple endodermal cell types, might be a valid alternative for the use of PSCs for creation of endodermal cell types.

Reprogramming can occur by the introduction of key transcription factors (TFs) as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) combined with a chromatin remodeling medium (CRM) induced expression of a number of definitive endoderm and early and late pancreatic marker genes. When CRM was omitted, endoderm/pancreatic marker genes were not induced. Furthermore, treatment with DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (5AZA) CRM did not affect gene expression changes, and when 5AZA was combined with TSA, no further increase in gene expression of endoderm, pancreatic endoderm, and endocrine markers was seen over levels induced with TSA alone. Interestingly, TSA-CRM did not affect expression of pluripotency and hepatocyte genes but induced some mesoderm transcripts. Upon removal of TSA-CRM, the endoderm/pancreatic gene expression profile returned to baseline. Our findings underscore the role epigenetic modification in transdifferentiation of one somatic cell into another. However, full reprogramming of fibroblasts to β-cells will require combination of this approach with TF overexpression and/or culture of the partially reprogrammed cells under β-cell specific conditions.