From November 13-16, researchers, doctors, and others participated in the American Association for the Study of Liver Diseases (AASLD)’s Annual Meeting, or The Liver Meeting Digital Experience. During the virtual conference, biopharmaceutical company Intercept Pharmaceuticals (“Intercept”) shared data from the Phase 3 REGENERATE clinical trial. During the trial, researchers analyzed obeticholic acid (OCA) as a treatment for patients with nonalcoholic steatohepatitis (NASH). Ultimately, researchers determined that OCA improved fibrosis in patients with NASH. Additionally, Intercept shared data on the importance on routine noninvasive tests (NITs) to identify patients with severe fibrosis so that they can be better treated.

OCA, NITs, and Liver Fibrosis

Intercept researchers sourced data from the double blind, placebo controlled Phase 3 REGENERATE trial. During the trial, researchers evaluated the safety, tolerability, and efficacy of OCA in patients with advanced liver fibrosis. In total, 2,480 patients enrolled in the clinical outcomes group. Researchers analyzed the safety of OCA for up to 37 months (3 years, 1 month). Patients who received OCA were given either a 10mg or 25mg dose. While side effects and adverse reactions were slightly higher in patients taking the higher dose, adverse reactions were generally not severe. Although three patients died during the course of the trial, none of the deaths were attributed to OCA therapy. Reported side effects included:

• Itching
• Higher levels of LDL cholesterol
• Gallstones

Patients receiving 25mg OCA daily showed improvement in liver fibrosis. Additionally, this same group of patients did not experience NASH progression. Intercept argues that using NITs to identify patients who have advanced liver fibrosis, and using that information to better treat these patients, can improve outcomes. NITs also help doctors better evaluate and understand how patients are responding to OCA treatment.

NITs are also an easier, more accessible, and less invasive option than liver biopsies. One presentation also shared at The Liver Meeting Digital Experience, under Abstract #1576, highlighted that only a small amount of patients ever receive a liver biopsy. As a result, it is an inefficient way to diagnose fibrosis.

Nonalcoholic Steatohepatitis (NASH)

Up to 25% of American citizens have nonalcoholic steatohepatitis (NASH), which occurs when fat accumulation in the liver causes inflammation and organ damage. Much like its name implies, NASH affects those who do not drink or drink very lightly. Those who are overweight, have diabetes, or have high cholesterol are at a higher risk of developing NASH. In some cases, NASH worsens over time, causing fibrosis (scarring). However, it is possible for NASH to not progressively worsen. If patients do have liver fibrosis, it can progress to cirrhosis, organ failure, and even death. Currently, there are no approved treatments for patients with NASH.

Symptoms include:

• Unintended weight loss
• Nausea and vomiting
• Easy bruising and bleeding
• Confusion
• Abdominal pain and swelling
• Jaundice (yellowing of the skin and eyes)
• Fatigue and general malaise
• Loss of appetite
• Pruritis (severe itching)
• Inflammation of the legs