Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc− have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.
Background
Alterations in body compositions are related to poor outcomes and the presence of complications in cirrhosis. However, no predictive tools combining all these anthropometric parameters are applicable in the clinical setting. We aimed to clarify the potential utility of body compositions and develop a nomogram incorporating any independent factor for prognosticating long‐term mortality in cirrhosis.
Methods
A total of 414 patients were randomized into primary (n = 274) and validation (n = 140) cohorts. X‐tile was performed to identify optimal cut points for stratifying participants. Multivariate Cox regression was performed, and nomogram incorporating body compositions were generated. The utility of developed models was evaluated by Harrell concordance index (C‐index), calibration curve, and decision curve analysis (DCA).
Results
Stratifying by X‐tilederived cut points, low skeletal muscle index (myopenia), high intramuscular adipose tissue content (myosteatosis), and the ratio of high visceral to subcutaneous adipose tissue area (adiposity) was independently associated with 3‐year mortality. A sex‐stratified nomogram incorporating anthropometric indices and clinical factors resulted in moderate discriminative accuracy, with a C‐index of 0.787 (95% CI, 0.736–0.838) and 0.789 (95% CI, 0.727–0.851) in males and females, respectively. The calibration curve showed predictive survival corresponding optimally with the actual outcomes. Our models were feasible in the clinical settings based on DCA. Similar results were observed in the validation cohort. Additionally, participants could be classified into 3 distinct risk groups by the nomogram.
Conclusions
Our proposed nomogram embedding body compositions rendered an individualized predictive tool for long‐term mortality in cirrhosis.
Background and Aims: Proton pump inhibitor (PPI) was widely used in cirrhotic patients with variceal bleeding empirically rather than evidence-based practice. We aimed to evaluate the plausible indication of PPI use in variceal bleeding cirrhotic patients and figure out whether it can decrease the re-bleeding rate after endoscopic therapy. Furthermore, we also investigated the association between PPI and bleeding-related mortality in these patients. Methods: We have searched in PubMed, Medline, Web of Science, Google Scholar, Cochrane and Embase prior to May 2019. Pooled OR and 95% CI were calculated by random-effects model. Results: A total of 11 original articles including 1,818 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use may decrease the re-bleeding rate after endoscopic therapy (OR 0.52, 95% CI 0.35–0.77). The conclusion was irrespective of study methods, endoscopic purpose and hemorrhage sites. However, the conclusion speculated that PPI should be prescribed >1 month. Meanwhile, PPI use may not impact the bleeding-related mortality. Conclusions: PPI, used for >1 month, can decrease re-bleeding rate after endoscopic therapy in cirrhotic patients for prophylaxis or emergency treatment purpose. No matter how long it takes, PPI use is not associated with bleeding-related mortality.
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