Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.
The thiazolidinediones, abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s.
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.
Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the name adopted in 2023 for the condition previously known as non-alcoholic fatty liver disease (NAFLD). This is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress towards it, but this progression may eventually lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.
Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, are a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.
Cenicriviroc is an experimental drug candidate for the treatment of HIV infection and in combination with Tropifexor for non-alcoholic steatohepatitis. It is being developed by Takeda and Tobira Therapeutics.
Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.
Intercept Pharmaceuticals, Inc. is an American biopharmaceutical company incorporated in 2002, focusing on the development of novel synthetic bile acid analogs to treat chronic liver diseases, such as primary biliary cirrhosis (PBC) now called primary biliary cholangitis, non-alcoholic fatty liver disease, cirrhosis, portal hypertension, primary sclerosing cholangitis and also the intestinal disorder, bile acid diarrhea.
Fexaramine is an investigational compound which acts as an agonist of the farnesoid X receptor (FXR), which is a bile acid-activated nuclear receptor that controls bile-acid synthesis, conjugation and transport, as well as lipid metabolism through actions in the liver and intestine.
Melissa Palmer is an American hepatologist. She is recognized for her research and treatment of hepatitis and liver disease. Palmer is the Chief Medical Officer of Gannex Pharma, a wholly owned company of Ascletis Pharma.
Nidufexor (LMB-763) is a drug which acts as a partial agonist of the farnesoid X receptor (FXR). It has reached Phase II clinical trials for the treatment of diabetic nephropathy and nonalcoholic steatohepatitis.
Cilofexor is a nonsteroidal farnesoid X receptor (FXR) agonist in clinical trials for the treatment of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). It is being investigated for use alone or in combination with firsocostat, selonsertib, or semaglutide. In rat models and human clinical trials of NASH it has been shown to reduce fibrosis and steatosis, and in human clinical trials of PSC it improved cholestasis and reduced markers of liver injury.
Resmetirom is an experimental drug for the treatment of non-alcoholic steatohepatitis (NASH). It is a selective agonist of thyroid hormone receptor-β which increases hepatic fat metabolism and reduces lipotoxicity.
Lanifibranor is a pan-PPAR receptor agonist and is the first medication that targets PPAR-alpha, PPAR-beta, and PPAR-gamma simultaneously. As of 2023, it is in a phase III trial for nonalcoholic steatohepatitis; its advantage over other drugs that are in phase III trials for the same condition is that it has shown improvements in both steatohepatitis and fibrosis.
Efocipegtrutide (HM15211) is a triple agonist of the glucagon, GIP, and glucagon-like peptide 1 receptors. It is being studied for obesity and nonalcoholic steatohepatitis.
Efruxifermin (AKR-001) is a fibroblast growth factor 21 (FGF21) analog developed to treat nonalcoholic steatohepatitis and type 2 diabetes.
EDP-305 is a non-bile acid farnesoid X receptor (FXR) agonist developed by Enanta Pharmaceuticals for non-alcoholic fatty liver disease. According to preclinical research CYP3A4 is the main enzyme used to metabolize the drug and there is a low potential for drug interactions.
HEC96719 is a tricyclic farnesoid X receptor agonist developed for non-alcoholic steatohepatitis.
