Corydalis and Drug-Induced Liver Injury: A Series of 2 Cases.

Corydalis is an herbal plant found in Asian countries. Research has demonstrated multiple health benefits. It has also been implicated in drug-induced liver injury. Cannabis dispensaries market a sleep aid which has corydalis as an active ingredient. We present 2 cases of corydalis-induced hepatotoxicity. An asymptomatic female patient exhibited a rise and fall of her transaminases coinciding with the consumption and rechallenge of this sleep aid. A man with symptoms consistent with liver dysfunction began taking the same sleep aid. With discontinuance, his liver function returned to normal. These 2 clinical cases provide evidence for corydalis-induced liver injury.

Heterogeneity of Hepatic Stellate Cells in Fibrogenesis of the Liver: Insights from Single-Cell Transcriptomic Analysis in Liver Injury.

BACKGROUND & AIMS: Liver fibrosis is a pathological healing process resulting from hepatic stellate cell (HSC) activation and the generation of myofibroblasts from activated HSCs. The precise underlying mechanisms of liver fibrogenesis are still largely vague due to lack of understanding the functional heterogeneity of activated HSCs during liver injury. Approach and Results: In this study, to define the mechanism of HSC activation, we performed the transcriptomic analysis at single-cell resolution (scRNA-seq) on HSCs in mice treated with carbon tetrachloride (CCl4). By employing LRAT-Cre:Rosa26mT/mG mice, we were able to isolate an activated GFP-positive HSC lineage derived cell population by fluorescence-activated cell sorter (FACS). A total of 8 HSC subpopulations were identified based on an unsupervised analysis. Each HSC cluster displayed a unique transcriptomic profile, despite all clusters expressing common mouse HSC marker genes. We demonstrated that one of the HSC subpopulations expressed high levels of mitosis regulatory genes, velocity, and monocle analysis indicated that these HSCs are at transitioning and proliferating phases at the beginning of HSCs activation and will eventually give rise to several other HSC subtypes. We also demonstrated cell clusters representing HSC-derived mature myofibroblast populations that express myofibroblasts hallmark genes with unique contractile properties. Most importantly, we found a novel HSC cluster that is likely to be critical in liver regeneration, immune reaction, and vascular remodeling, in which the unique profiles of genes such as Rgs5, Angptl6, and Meg3 are highly expressed. Lastly, we demonstrated that the heterogeneity of HSCs in the injured mouse livers is closely similar to that of cirrhotic human livers. CONCLUSIONS: Collectively, our scRNA-seq data provided insight into the landscape of activated HSC populations and the dynamic transitional pathway from HSC to myofibroblasts in response to liver injury.