New Rat Model of Advanced Non-Alcoholic-Steatohepatitis-Cirrhosis Developing Acute-on-Chronic-Liver failure

Introduction Over the last decade non-alcoholic-steatohepatitis (NASH) induced liver cirrhosis has markedly increased. Especially in the United States NASH and obesity are associated with the development of Acute-on-chronic liver failure (ACLF) and high short term mortality. In these patients especially proven bacterial infections and bacterial translocation are thought to precipitate the acute decompensation (AD) and ACLF. Thus, the aim of this study was to develop ACLF models in NASH induced liver cirrhosis.

Methods Liver cirrhosis was induced by administration of high fat western diet (WD) and additional intraperitoneal CCl4 injections twice per week combined with phenobarbital for 7 weeks. The precipitating events bacterial translocation and infections were mimicked by the repetitive lipopolysaccharide (LPS) injections and transnasal stool inoculation (TNI), respectively. Organ dysfunction and failures were assessed by histology, blood parameters, gene expression levels, invasive pressure measurement and neurological behavior tests and categorized according to the adapted CLIF-SOFA score.

Results Repetitive LPS injections and TNI induced liver, kidney and circulatory failure in NASH rats as assessed by histology, blood parameters, gene expression levels and invasive pressure measurement. Besides liver and kidney failure, NASH animals developed severe respiratory and cerebral failure, which is shown by decreased oxygen saturation and pathologic neurological tests after bacterial translocation and infection.

Conclusion The models of bacterial translocation and infection as precipitating events in NASH rats induce AD and ACLF and mimic the human situation and may be useful in testing pharmacologic treatments.

Publication History

Article published online:
26 January 2022