The Preventive Role of Hydrogen-Rich Water in Thioacetamide-Induced Cholangiofibrosis in Rat Assessed by Automated Histological Classification.

Cholangiofibrosis is a controversial intrahepatic cholangial lesion that precedes the development of cholangiocarcinoma. Here, we demonstrate that molecular hydrogen (H) can be used to effectively prevent cholangiofibrosis. The safety and quality of life (QOL) of rats was firstly evaluated. H was administered to rats subjected to thioacetamide (TAA)-induced cholangiofibrosis throughout the whole process. Then, rats were administrated with TAA for 3 months and then followed by H intervention. Rat livers were harvested and assessed by light microscopy and convolutional neural network. RNA-seq was performed to analyze the genetic changes in these animal models. Continuous use of H-rich water was safe and improved QOL.The incidence and average number of cholangiofibrosis in the liver were higher in the TAA group (100%, 12.0 ± 10.07) than that in the H group (57.1%, 2.86 ± 5.43). The AI algorithm revealed higher Alesion/Aliver in the TAA group (19.6% ± 9.01) than that in the H group (7.54% ± 11.0). RNA-seq analysis revealed that H results in a decline in glycolysis. Moreover, in the third experiment, the incidence of microscopic or suspicious tumors and the ratio of liver lesions was decreased after long-term use of H (12.5%, 0.57% ± 0.45) compared with untreated group (100%, 0.98% ± 0.73). A number of intestinal microbiota was changed after H usage, including clostridiaceae_1, ruminococcus, turicibacter, coriobacteriales, actinobacteria, and firmicutes_bacterium. Hydrogen-rich water protects against liver injury and cholangiofibrosis and improved quality of life partially through regulating the composition of intestinal flora.