obeticholic-acid and aramchol

Nonalcoholic fatty liver disease (NAFLD) is recognized as a global health problem and as a common cause of chronic liver disease. Nonalcoholic steatohepatitis (NASH) carries an increased risk for development of advanced liver disease. Lifestyle modifications with diet and exercise have been the initial management recommendation. However, these changes are difficult to achieve and sustain overtime. There are pharmacologic agents being considered for treatment of NASH. Some target insulin resistance and others focus on oxidative stress, inflammation, apoptosis, and fibrosis. There is a great deal of efforts to develop therapeutic regimens for patients with NASH and NASH with significant fibrosis.

Topics: Antioxidants; Chenodeoxycholic Acid; Cholic Acids; Diet Therapy; Exercise; Free Radical Scavengers; Humans; Hypoglycemic Agents; Life Style; Non-alcoholic Fatty Liver Disease; Pentoxifylline; Vitamin E

Nonalcoholic fatty liver disease is the most common cause of liver disease in the United States. There are no drug therapies approved for the treatment of nonalcoholic steatohepatitis (NASH). Multiple different pathways are involved in the pathogenesis and each can be the target of the therapy. It is possible that more than 1 target is involved in disease development and progression. Multiple clinical trials with promising agents are underway. Because NASH is a slowly progressive disease and treatment likely to be of prolonged duration, acceptance and approval of any agent will require information on long-term clinical benefits and safety.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antioxidants; Caspase Inhibitors; Chenodeoxycholic Acid; Cholic Acids; Fatty Acids, Omega-3; Humans; Incretins; Insulin Resistance; Liraglutide; Liver X Receptors; Non-alcoholic Fatty Liver Disease; Pectins; Peroxisome Proliferator-Activated Receptors; Receptors, Cytoplasmic and Nuclear; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

In recent years, there has been an increasing number of clinical trials for the treatment of nonalcoholic steatohepatitis (NASH). People living with human immunodeficiency virus (PLWH) are commonly excluded from these studies, usually due to concerns over drug-drug interactions associated with antiretroviral therapy. The Steatohepatitis in HIV Emerging Research Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between human immunodeficiency virus and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of drug-drug interactions between antiretroviral therapy and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL-3196), which are currently in phase 3 trials for the treatment of NASH, are reviewed. A model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a subpopulation within studies.

Topics: Anti-Retroviral Agents; Chalcones; Chenodeoxycholic Acid; Cholic Acids; Clinical Trials, Phase III as Topic; Drug Interactions; HIV Infections; Humans; Imidazoles; Non-alcoholic Fatty Liver Disease; Propionates; Pyridazines; Sulfoxides; Uracil