Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis.

The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of "NASH-associated macrophages" can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.

Randomized clinical trial comparing oral prednisone (50 mg) with placebo before laparoscopic cholecystectomy.

BACKGROUND: Intravenous administration of dexamethasone 90 min before laparoscopic cholecystectomy improves surgical outcome but may be impractical. The objective of this study was to assess the clinical efficacy of oral self-administration of prednisone 2 h before ambulatory laparoscopic cholecystectomy. METHODS: In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain 24 h after surgery and secondary outcomes were fatigue and malaise 24 h after surgery. Outcome parameters were registered before operation, on the day of operation, and the following two days. Analgesic and antiemetic requirements were registered, and nausea and vomiting were assessed twice within the first 24 h. Side-effects and 30-day follow-up for morbidity were registered. RESULTS: Data from 184 patients were available for statistical analysis. There were no significant differences in side-effects or complications between the surgical groups (P > 0.05). No significant intergroup differences in 24-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). CONCLUSION: There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy.