Feb. 20, 2018
نطاق مرض الكبد الدهني غير الناجم عن شرب الكحول (NAFLD)
يتضمن هذا النطاق من الحالات، التهاب الكبد الدهني غير الناجم عن شرب الكحول (NASH)، وتليف الكبد، وسرطان الخلايا الكبدية، وفشل الكبد في مراحله الأخيرة.
First described in 1980, nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the United States. This spectrum of conditions is characterized by fatty infiltration of the liver and includes nonalcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma and end-stage liver failure.
NAFLD is becoming more prevalent, particularly in Western countries as obesity rates rise in all age groups. Experts predict that this diagnosis will become the leading cause of liver transplantation.
The search for effective treatments for NAFLD and NASH has benefitted from advances in understanding the pathophysiology of these conditions. The list that follows highlights some of the emerging treatment options that Mayo research teams and collaborators are currently exploring.
Led by Elizabeth J. Carey, M.D., a specialist in gastroenterology and hepatology at Mayo Clinic's campus in Arizona, this phase III trial is designed to evaluate the safety and effectiveness of obeticholic acid (OCA) treatment compared with placebo in patients with noncirrhotic NASH with stage 2 to 3 liver fibrosis. OCA is a modified bile acid that is a farnesoid X receptor (FXR) agonist. Conducted at Mayo Clinic's campuses in Arizona and Minnesota, this trial looks at both tissue structure improvement and liver-related clinical outcomes.
Bashar A. Aqel, M.D., a specialist in gastroenterology and hepatology at Mayo Clinic's campus in Arizona is the primary investigator for two phase III trials focusing on selonsertib (SEL; GS-4997). Selonsertib is a small molecule inhibitor of apoptosis signal-regulating kinase I (ASK). Conducted in both Arizona and Minnesota, these two trials evaluate whether selonsertib can cause fibrosis regression and reduce associated complications in two populations: adults with NASH-related stage 3 liver disease and adults with NASH-related cirrhosis.
Focusing on the treatment of decompensated NASH cirrhosis, this multicenter phase II trial is led by Hugo E. Vargas, M.D., a gastroenterologist and hepatologist specializing in viral hepatitis and liver transplantation at Mayo Clinic's campus in Arizona. Dr. Vargas and colleagues are examining the efficacy of this small molecule caspase inhibitor in improving event-free survival, based on a composite clinical endpoint defined by all-cause mortality, new decompensation events and MELD score progression. This trial is being conducted at Mayo Clinic's campuses in Arizona and Minnesota.
Bristol-Myers Squibb (BMS)-985036
BMS-986036 is an investigational pegylated analogue of human fibroblast growth factor 21. Mayo researchers plan to test the safety and efficacy of this drug in two separate populations: adults with NASH and stage 3 liver fibrosis and adults with compensated liver cirrhosis.