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.
Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and consequently energy intake, increasing energy expenditure, redirecting nutrients from adipose to lean tissue, or interfering with the absorption of calories.
Renzapride is a prokinetic agent and antiemetic which acts as a full 5-HT4 agonist and partial 5-HT3 antagonist. It also functions as a 5-HT2B antagonist and has some affinity for the 5-HT2A and 5-HT2C receptors.
Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a type of chronic liver disease. This condition is diagnosed when there is excessive fat build-up in the liver, and at least one metabolic risk factor. When there is also increased alcohol intake, the term MetALD, or metabolic dysfunction and alcohol associated/related liver disease is used, and differentiated from alcohol-related liver disease (ALD) where alcohol is the predominant cause of the steatotic liver disease. The terms non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis have been used to describe different severities, the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress to it, but this progression may eventually lead to complications, such as cirrhosis, liver cancer, liver failure, and cardiovascular disease.
Oleoyl-estrone (OE), or estrone 3-oleate, is a fatty acid ester of estrone. It is a naturally circulating hormone in animals, including humans. It was studied as a potential weight-loss drug, but failed to show benefit in clinical trials. It was first reported in 1996 to cause a body fat loss effect in rats in the International Journal of Obesity and Related Metabolic Disorders. The animal research has all been conducted by the Nitrogen-Obesity Research Group of the University of Barcelona.
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a condition of the liver in which the normal functioning tissue, or parenchyma, is replaced with scar tissue (fibrosis) and regenerative nodules as a result of chronic liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regenerating hepatocytes can replace the parenchyma, causing increased resistance to blood flow in the liver's capillaries—the hepatic sinusoids—and consequently portal hypertension, as well as impairment in other aspects of liver function. The disease typically develops slowly over months or years.
Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective. Depending on the severity of symptoms, it may be recognised as a disability in the United Kingdom under the Equality Act 2010.
Naldemedine, sold under the brand name Symproic in the US and Rizmoic in the European Union, is a medication that is used for the treatment of opioid-induced constipation in adults who have previously been treated with a laxative in the European Union, or to treat opioid induced constipation in adults with chronic non-cancer pain in the US. It is a peripherally acting μ-opioid receptor antagonist and was developed by Shionogi. Clinical studies have found it to possess statistically significant effectiveness for these indications and to be generally well tolerated, with predominantly mild to moderate gastrointestinal side effects. Effects indicative of central opioid withdrawal or impact on the analgesic or miotic effects of co-administered opioids have only been observed in a small number of patients.
Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood.
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.
Aramchol is an investigational drug being developed by Galmed Pharmaceuticals as a first-in-class, potentially disease modifying treatment for nonalcoholic steatohepatitis, or NASH, a more advanced condition of non-alcoholic fatty liver disease.
Mamun Al Mahtab is a Bangladeshi hepatologist. With 290 publications in national and international peer-reviewed journals to his credit, Mahtab works as the head, Division of Interventional Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU).
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.
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, sold under the brand name Rezdiffra, is a medication used for the treatment of noncirrhotic nonalcoholic steatohepatitis. It is a thyroid hormone receptor beta (NR1A2) agonist.
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.
Pegozafermin (BIO89-100) is a long-acting, glycopegylated FGF21 analog developed for the treatment of nonalcoholic steatohepatitis and hypertriglyceridemia.
PXL065 (d-R-pioglitazone) is a drug candidate for the treatment of nonalcoholic steatohepatitis (NASH). It is the deuterium-stabilized (R)-enantiomer of pioglitazone which lacks PPARγ agonist activity and the associated side effects of weight gain and edema. PXL065 (formerly known as DRX-065) has demonstrated preclinical efficacy for both NASH and X-linked adrenoleukodystrophy (X-ALD). In 2022, it successfully completed a 9 month Phase 2 trial in biopsy-proven NASH patients where it met the primary endpoint for reduction in liver fat without weight gain or edema.
Rencofilstat (CRV431) is a pan-cyclophilin inhibitor and analog of cyclosporine A developed for nonalcoholic steatohepatitis and hepatocellular carcinoma.
Aldafermin is a fibroblast growth factor 19 (FGF19) analogue developed for non-alcoholic steatohepatitis.
