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Abstract Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases. Graphical Abstract

Abstract Background A precise evaluation of liver reserve function in patients with hepatic alveolar echinococcosis (HAE) prior to hepatectomy could substantially increase the success rate of the operation and reduce the incidence of postoperative complications. The present study aimed to investigate the significance of the indocyanine green retention test at 15 min (ICG-R15) and the Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting severe posthepatectomy liver failure (PHLF) and postoperative mortality in HAE patients undergoing liver resection. Methods A total of 105 HAE patients undergoing hepatectomy were enrolled in this study. The value of each variable in predicting severe PHLF was evaluated by univariate and multivariate logistic regression analyses. The area under the receiver operating characteristic (ROC) curves (AUC) were calculated to evaluate the predictive ability of the Child–Pugh grade, ICG-R15, and ALICE grading system. Also, patients were classified using the optimal cutoff value for ICG-R15 and different ALICE grades, and the incidence of severe PHLF and postoperative mortality were compared with the predicted values. Results Out of the 105 HAE patients enrolled in this study, 34 patients (32.4%) developed severe PHLF. The ALICE grade and operative time were identified as independent predictors of severe PHLF. According to ROC analysis, the AUCs of the Child–Pugh grade, ICG-R15, and ALICE grade for predicting severe PHLF were 0.733 (95% confidence interval (CI), 0.637–0.814), 0.823 (95% CI, 0.737–0.891), 0.834 (95% CI, 0.749–0.900). The incidence of severe PHLF and postoperative 90-day mortality in patients with ICG-R15 > 7.2% were significantly higher than those with ICG-R15 ≤ 7.2% (P

Abstract Background Gynura segetum (GS) is widely used in medical care and in community settings in China as the herbal remedy. It is widely thought to have antiphlogistic properties and pain relief in traditional Chinese medicine. It has been reported that GS can cause chronic drug-induced liver injury (DILI), manifested as hepatic sinusoid obstruction syndrome (HOSO). But case reports of acute DILI developing acute liver failure (ALF) due to GS are extremely rare. Case presentation We report a case of a 63-year-old female patient with hepatolithiasis for more than 6 years. There were no deterioration of liver function and no history of viral liver disease, autoimmune liver disease, blood transfusion or surgical allergy before operation. ALF and grade II liver encephalopathy occurred after partial hepatectomy. To follow up the medical history, the patient has been taking GS (Tusanqi) for a year and a half. The causality assessment was done by the updated Roussel Uclaf Causality Assessment Method, and the possibility of DILI caused by GS as highly probable for the score was 6 points. Excluding other causes, a diagnosis of DILI-associated ALF was established. After symptomatic support and artificial liver support system (ALSS) treatment, the clinical symptoms and signs of the patients were significantly improved. After discharge, the liver function of the patients returned to normal. Conclusions Based on this rare case of severe liver injury, we recommend that timely prevention, identification, and appropriate management of DILI is essential for patients with a history of taking GS and other hepatotoxic drugs, and careful monitoring of liver function for patients with DILI could avoid ALF as far as possible.