The novel findings of this study are: (i) increased hepatic expression of caspase-4 is a feature of acutely decompensated cirrhosis and correlates with disease severity, (ii) hepatic expression of caspase-11 is also upregulated in a mouse model of advanced liver fibrosis, (iii) hepatic expression of the cleaved fragment of GSDMD, the effector protein of the pyroptosis pathway, is increased in mice with liver fibrosis and multi-organ injury, (iv) Casp11–/– mice with advanced liver fibrosis are protected from excess hepatocyte death and multi-organ injury. This evidence concerns the gene CASP4 and Hepatic fibrosis.