Hepatocellular carcinoma (HCC) represents a worryingly increasing cause of malignancy-related mortality, while Metabolic Associated Fatty Liver Disease (MAFLD) is going to become its most common cause in the next decade. Understanding the complex underlying pathophysiology of MAFLD-related HCC can provide opportunities for successful targeted therapies. Of particular interest in this sequela of hepatopathology is cellular senescence, a complex process characterised by cellular cycle arrest initiated by a variety of endogenous and exogenous cell stressors. A key biological process in establishing and maintaining senescence is oxidative stress, which is present in multiple cellular compartments of steatotic hepatocytes. Oxidative stress-induced cellular senescence can change hepatocyte function and metabolism, and alter, in a paracrine manner, the hepatic microenvironment, enabling disease progression from simple steatosis to inflammation and fibrosis, as well as HCC. The duration of senescence and the cell types it affects can tilt the scale from a tumour-protective self-restricting phenotype to the creator of an oncogenic hepatic milieu. A deeper understanding of the mechanism of the disease can guide the selection of the most appropriate senotherapeutic agent, as well as the optimal timing and cell type targeting for effectively combating HCC.

Hepatocarcinogenesis is a long process with a complex pathophysiology. The current therapeutic options for HCC management, during the advanced stage, provide short-term survival ranging from 10–14 months. Autophagy acts as a double-edged sword during this process. Recently, two main autophagic pathways have emerged to play critical roles during hepatic oncogenesis, macroautophagy and chaperone-mediated autophagy. Mounting evidence suggests that upregulation of macroautophagy plays a crucial role during the early stages of carcinogenesis as a tumor suppressor mechanism; however, it has been also implicated in later stages promoting survival of cancer cells. Nonetheless, chaperone-mediated autophagy has been elucidated as a tumor-promoting mechanism contributing to cancer cell survival. Moreover, the autophagy pathway seems to have a complex role during the metastatic stage, while induction of autophagy has been implicated as a potential mechanism of chemoresistance of HCC cells. The present review provides an update on the role of autophagy pathways in the development of HCC and data on how the modulation of the autophagic pathway could contribute to the most effective management of HCC.

The indisputable increase in non-Alcoholic Fatty Liver Disease (NAFLD) prevalence, has consequently led to an increase in Hepatocellular Carcinoma (HCC) and liver-related mortality worldwide. Twent...

Clinical practice has inadvertently changed after the COVID-19 pandemic and currently the need to provide sustainable surgical services is more pressing than ever. The National Health Service has committed to a long-term efficient plan to reduce carbon footprint but there is no detailed plan for surgical practice, the domain that contributes the most to hospital-derived pollution. A series of consecutive steps and measures ought to be taken, starting from a hybrid approach quantifying surgically attributed carbon footprint. Then, a variety of suggested measures can be widely discussed and accordingly applied on a wider or more local level. Appropriate training should always precede implementing new practices to ensure that staff is familiar with these. These measures cover a broad range and should be arranged on a patient-centred basis from preoperative preconditioning to an effective follow-up. The need for more intense research and implementation of enhanced recovery protocols is widely discussed. Also, the necessity of green research and reinvestment of materials and resources is highlighted. A change of philosophy from a cradle-to-grave approach to a repurposing approach is suggested. We are confident that a new era is dawning in surgical practice and teamwork is the key for providing greener surgical services.

The increasing prevalence of the spectrum of Steatotic Liver Disease (SLD), including Metabolic-Associated Steatotic Liver Disease (MASLD), Metabolic-Associated Steatohepatitis (MASH), and progression to Cirrhosis and Hepatocellular Carcinoma (HCC) has led to intense research in disease pathophysiology, with many studies focusing on the role of iron. Iron overload, which is often observed in patients with SLD as a part of metabolic hyperferritinaemia (MHF), particularly in the reticuloendothelial system (RES), can exacerbate steatosis. This imbalance in iron distribution, coupled with a high-fat diet, can further promote the progression of SLD by means of oxidative stress triggering inflammation and activating hepatic stellate cells (HSCs), therefore leading to fibrosis and progression of simple steatosis to the more severe MASH. The influence of iron overload in disease progression has also been shown by the complex role of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. Ferroptosis depletes the liver’s antioxidant capacity, further contributing to the development of MASH, while its role in MASH-related HCC is potentially linked to alternations in the tumour microenvironment, as well as ferroptosis resistance. The iron-rich steatotic hepatic environment becomes prone to hepatocarcinogenesis by activation of several pro-carcinogenic mechanisms including epithelial-to-mesenchymal transition and deactivation of DNA damage repair. Biochemical markers of iron overload and deranged metabolism have been linked to all stages of SLD and its associated HCC in multiple patient cohorts of diverse genetic backgrounds, enhancing our daily clinical understanding of this interaction. Further understanding could lead to enhanced therapies for SLD management and prevention.