Abstract: The present invention derives from the unexpected finding that pyroptosis is a novel biomarker and target for therapy in liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Gasdermin D (GSDMD), caspase 4, caspase 5, or Interleukin 1 alpha (IL-1?) can be detected and quantified in serum or plasma, and used as biomarkers for outcome in liver failure such as acute liver failure (ALF) and ACLF and other diseases involving aberrant pyroptosis. By antagonising GSDMD, caspase 4, caspase 5 or Interleukin 1 alpha (IL-1?) many of the unwanted consequences or symptoms of liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1? that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF.

Abstract: The present invention derives from the unexpected finding that necroptosis is a novel biomarker and target for therapy in patients with liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). RIPK1, MLKL or RIPK3 can be detected and quantified in serum or plasma, and used as a biomarker for outcome in ACLF and other diseases involving aberrant necroptosis. By antagonising RIPK1, MLKL or RIPK3 many of the unwanted consequences or symptoms of acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of RIPK1, MLKL and RIPK3 that may be used in the treatment or prevention of ACLF. The present invention utilises these findings to identify and provide antagonists of RIPK1, MLKL or RIPK3 that may be used in the treatment or prevention of aberrant necroptosis in the kidney, brain, liver or other organ of the body.

Abstract: The invention relates to the treatment of an individual suffering from a cytokine storm syndrome. It relates to methods for the treatment of such an individual and to systems and devices for use in such treatment.

Abstract: The present invention derives from the unexpected finding that the combination of the stem cell mobilisers such as G-CSF and antagonists of TLR4 is beneficial to patients with liver failure, such as acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). The present invention utilises these findings to provide stem cell mobilisers such as G-CSF and antagonists of TLR4 that may be used in the treatment or prevention of liver failure, such as ALF or ACLF. Also encompassed by the invention is the provision of a stem cell and an antagonist of TLR4 for use in the treatment or prevention of liver failure, such as ALF or ACLF.

Abstract: The present invention relates to a method of predicting acute decompensation (AD) and/or the development of acute-on-chronic liver failure (ACLF) in a patient having the condition, or at risk of having the condition, using heart-rate variability (HRV) as a marker.

Abstract: Disclosed herein are methods of treating and/or preventing portal hypertension and/or restoring liver function using L-ornithine phenylacetate.

Abstract: Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

Abstract: The present invention derives from the unexpected finding that necroptosis is a novel biomarker and target for therapy in patients with liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). RIPK1, MLKL or RIPK3 can be detected and quantified in serum or plasma, and used as a biomarker for outcome in ACLF and other diseases involving aberrant necroptosis. By antagonising RIPK1, MLKL or RIPK3 many of the unwanted consequences or symptoms of acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of RIPK1, MLKL and RIPK3 that may be used in the treatment or prevention of ACLF. The present invention utilises these findings to identify and provide antagonists of RIPK1, MLKL or RIPK3 that may be used in the treatment or prevention of aberrant necroptosis in the kidney, brain, liver or other organ of the body.

Abstract: The present invention derives from the unexpected finding that pyroptosis is a novel biomarker and target for therapy in liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Gasdermin D (GSDMD), caspase 4, caspase 5, or Interleukin 1 alpha (IL-1?) can be detected and quantified in serum or plasma, and used as biomarkers for outcome in liver failure such as acute liver failure (ALF) and ACLF and other diseases involving aberrant pyroptosis. By antagonising GSDMD, caspase 4, caspase 5 or Interleukin 1 alpha (IL-1?) many of the unwanted consequences or symptoms of liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1? that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF.

Abstract: The present invention derives from the finding that increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction.

Abstract: Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

Abstract: The present invention derives from the finding that increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction.

Abstract: The present invention relates to use of ornithine in the manufacture of a medicament for use in combination with at least one of phenylacetate and phenylbutyrate for preventing or treating liver decompensation or hepatic encephalopathy. The invention also relates to use of at least one of phenylacetate and phenylbutyrate in the manufacture of a medicament for use in combination with ornithine for preventing or treating liver decompensation or hepatic encephalopathy.

Abstract: Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

Abstract: The invention provides porous carbon particles for use in the treatment or prevention of liver disease, wherein at least 20% of the total pore volume is made up of pores having a mean diameter of from 2 to 200 nm and/or wherein the particles comprise micropores of diameter 2 nm or less and small macropores of diameter 50 nm to 500 nm, but substantially no mesopores of diameter greater than 2 nm and less than 50 nm, and substantially no large macropores of diameter greater than 500 nm.

Abstract: Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

Abstract: The present invention derives from the finding that increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction.

Abstract: Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

Abstract: Disclosed herein are methods of treating and/or preventing portal hypertension and/or restoring liver function using L-ornithine phenylacetate.

Abstract: The present invention derives from the finding that increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction.