NASH is expected to be the leading cause of liver transplantation in the U.S. as early as 2020
Nonalcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that occurs when excessive amounts of fat build up in the liver, damaging hepatocytes. NASH is driven by inflammation, which results in fibrosis.
NASH is usually a silent disease with few or no symptoms. As a result, it can progress for years – or even decades – undetected. As the liver damage becomes more severe, patients with NASH can progress to serious, life-threatening clinical outcomes, including decompensated cirrhosis (in which the liver is permanently damaged and scarred and unable to function properly), end-stage liver failure and its complications, hepatocellular carcinoma (HCC), the need for liver transplantation, and even death.
NASH is the fastest-growing reason for liver transplantation in the United States, and the supply of donor organs cannot keep up with the demand. NASH has already surpassed alcoholic liver disease as a reason for liver transplantation in the United States.
More common in people with obesity and type 2 diabetes
Many people with NASH struggle with other health conditions, including:
People who have metabolic syndrome also are at greater risk of developing NASH. This is a cluster of conditions that occur together in an individual, and can include high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.
The gold standard to confirm the diagnosis of NASH is a liver biopsy, in which a small sample of the liver is removed and examined. New non-invasive technologies that can detect fibrosis are becoming more broadly available, but these are not yet approved or included in treatment guidelines.
Consequences of advanced fibrosis
Fibrosis is measured on a scale of 0 to 4 and the risk of liver-related mortality increases significantly with increasing fibrosis stage; therefore, individuals with advanced fibrosis are at a much higher risk of developing liver-related complications, including progression to cirrhosis, HCC, liver failure, liver transplantation and death. In one study evaluating NASH patients with stage 3 fibrosis, more than one in five progressed to cirrhosis in less than 2 years. Additionally, patients with fibrosis stage 3 had an approximately two times greater risk of liver-related mortality, while patients with fibrosis stage 4 had an approximately four times greater risk.
Because patients with NASH and advanced fibrosis are at the greatest risk of progressing to severe liver-related outcomes, a comprehensive treatment approach is needed that stabilizes or reverses fibrosis and improves the underlying features of NASH – steatosis, hepatocyte ballooning and inflammation.
New treatments are urgently needed
The treatment of NASH is currently limited to lifestyle changes and specific treatment of comorbidities. People with NASH are advised to make dietary changes and exercise to lose weight, and to avoid heavy alcohol consumption.
At the present time, no pharmacologic treatments are approved to treat NASH, but clinical trials of investigational drugs are under way.
NASH is a complex disease, but our understanding of its underlying causes has increased in recent years. Scientific research is now exploring ways to stabilize or reverse fibrosis in patients with NASH by comprehensively impacting the key pathways that underlie the disease.
OCA is in Phase 3 clinical development for NASH
We are currently evaluating obeticholic acid (OCA) as a potential treatment for NASH. OCA, a modified version of a bile acid, is currently the only investigational therapy in this disease that has received Breakthrough Therapy designation for NASH. We are studying it in two ongoing Phase 3 clinical trials, which currently include the largest cohort of patients with NASH.
REGENERATE (Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment) is a randomized, double-blind, placebo-controlled, multicenter trial. It is assessing the safety and potential benefit of OCA on liver-related clinical outcomes in NASH patients with fibrosis. Read more about REGENERATE here.
REVERSE (Randomized Phase 3 Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects with Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis) is a randomized, double-blind, placebo-controlled, multicenter trial. It is evaluating the safety and efficacy of OCA in histological improvement in fibrosis with no worsening of NASH. For more information, visit ClinicalTrials.gov (Identifier: NCT03439254).
OCA has not been approved for the treatment of NASH by any regulatory authority in any geography and is considered an investigational treatment for this indication.