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.
Bicyclol, a novel synthetic antihepatitis drug, has been shown to protect against liver injury via various pharmacological activities. The purpose of the current study was to further investigate the protective effect of bicyclol against carbon tetrachloride (CCl 4)-induced acute liver injury (ALI) and its underlying molecular mechanism, particularly autophagic machinery, antioxidative, and anti-inflammatory potentials. Our results found that treatment with bicyclol significantly reduced CCl 4-induced hepatotoxicity by alleviating histopathological liver changes, decreasing the alanine transaminase levels, promoting autophagic flux, attenuating the expression of inflammatory cytokines, and modulating oxidative markers. Furthermore, bicyclol efficiently induced the conversion of LC3 and enhanced the liver expressions of ATG7 and Beclin-1. Meanwhile, bicyclol induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and p62. These protective effects may be mediated by activation of AMP-activated protein kinase and inhibition of mTOR or MAPK signaling pathways. Taken together, our study firstly suggests that bicyclol has protective potential against CCl 4-induced hepatotoxicity, which might be closely associated with induction of autophagy, concomitant anti-oxidative stress, and anti-inflammatory response.
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