From the Editor’s Desk...

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Targeting the liver clock improves fibrosis by restoration of TGF-β signalling

The circadian clock (CC) regulates several functions in the liver and perturbations have been shown to be associated with liver disease. Crouchet, Dachraoui and coworkers studied the functional role of CC as a driver and therapeutic target in liver fibrosis. The authors show that CC oscillators are present in both hepatocytes and stellate cells, with the hepatocyte CC influencing stellate cell gene expression. They also demonstrated that the CC oscillator modulates the expression of TGF-β

A new mouse model resembling cholangiocellular carcinoma development in chronic cholangiopathies

Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma (CCA), which is difficult to diagnose and is associated with a high mortality rate. Huang, Wei and coworkers aimed to develop a mouse model of PSC-associated CCA using Mdr2^-/- mice, which exhibit a PSC-like cholestatic injury pattern, and injected them with proto-oncogenes AKT and Yap to induce tumour formation. They found that hydrodynamic tail vein injection of these genes led to robust tumour growth,

Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of MASLD

Efficacy in animal models of metabolic dysfunction-associated steatotic liver disease (MASLD) often fails to translate into efficacy in humans, thereby requiring adjunctive systems to bridge this divide. In this issue, Kwon and coworkers demonstrate the utility of a cryopreserved primary human hepatocyte model in testing putative therapies. Their model recapitulated aspects of human MASLD in response to incubation with free fatty acids, which were corrected by firsocostat. These data provide

Long-term outcomes after HOPE in a real-world setting (HOPE-REAL study)

Preservation by liver machine perfusion is increasingly being implemented in clinical practice and helps overcome organ shortages by increasing utilisation of high-risk livers that need optimisation and assessment before transplantation. However, data on long-term outcomes are scarce. In this issue, Eden and coworkers report on recipient outcomes after liver transplantation (LT) with hypothermic oxygenated machine perfusion (HOPE) at 22 European LT centres between 2012 and 2021 (the HOPE-REAL

Patient-reported outcomes in chronic hepatitis delta: an exploratory analysis of the phase III MYR301 trial of bulevirtide

The study by Buti and coworkers investigated patient-reported outcomes (PROs) in the bulevirtide 301 registration trial for hepatitis D. Bulevirtide is a novel drug which blocks entry of HBsAg into hepatocytes and was fully approved by the EMA for the treatment of hepatitis D in 2023. The primary outcome of that pivotal study was published in the NEJM. However, it was unclear to what extent PROs also improve with this treatment. About half of the patients had cirrhosis and most had significant

Porto-sinusoidal vascular liver disorder with portal hypertension: natural history and long-term outcomes

The natural history of patients with portal hypertension due to porto-sinusoidal vascular disorder (PSVD) has not been fully described. In this month’s issue, Magaz, Giudicelli-Lett and coworkers present the results of a retrospective study in 587 patients from a multicentre cohort of patients with PSVD, of whom 64% were compensated at inclusion. Over a 5-year follow-up, 15% had first-time bleeding, and 18% experienced rebleeding. The 5-year cumulative incidence of new or worsening ascites was

Impact of pre-transplant ICI use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis

ICIs have revolutionised the treatment landscape of hepatocellular carcinoma (HCC), but the impact of pre-transplant ICI on allograft rejection, HCC recurrence, and overall survival is not known. Rezaee-Zavareh and coworkers report the results of a systematic review and individual patient data meta-analysis of 30 studies including 91 patients. Over a follow-up of 690.0 days, 24 patients had allograft rejections, 9 had HCC recurrences, and 9 died. Median time to rejection was 10.0 days, and

Philip Newsome∗ at Roger Williams Institute of Liver Studies and King’s Health Partner’s Centre for Translational Medicine, King’s College London, London, United Kingdom.