Non-Alcoholic Steatohepatitis (NASH)

Overview of NASH

NASH is a severe type of non-alcoholic fatty liver disease, or NAFLD. NAFLD is the most common liver disease and is associated with obesity and type-2 diabetes. It is characterized by the accumulation of fat in the liver with no other apparent causes. NASH occurs when the accumulation of liver fat is accompanied by inflammation and cellular damage. The inflammation can lead to fibrosis (scarring) of the liver and eventually progress to cirrhosis, portal hypertension, liver cancer and eventual liver failure. Once the disease advances beyond NASH to these life-threatening conditions, liver transplantation is the only alternative.

Epidemiology of NASH

The rising prevalence of obesity-related disorders has contributed to a rapid rise in the prevalence of NASH. In the United States, NASH affects an estimated 9 million to 15 million people, or 3 to 5 percent of the population, with similar prevalence in the EU and China. Driven by the obesity epidemic, NASH is projected to become the leading cause of liver transplants by the year 2020.

Treatment

Currently no therapies are approved for the treatment of NASH

Recent scientific advances in understanding NASH have led to the development of investigational drugs with the potential to address the disease through various mechanisms, but Tobira believes that it is the only developer that is targeting the immuno-inflammatory pathways responsible for fibrosis in NASH with CCR2/CCR5 inhibition.

Symptoms

NASH is often termed a silent killer as there are minimal symptoms. In later stages of the disease patients report symptoms of fatigue, weight loss and weakness.

The highest prevalence of NASH is in men between the ages of 40 and 65. Factors that can increase the likelihood of suffering from NASH includes increasing age, obesity, and type-2 diabetes.

Diagnosis

In order to definitively confirm NASH a liver biopsy is required. There are a number of factors that may be helpful in determining if you have NASH.

  • A history of abnormal levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
  • Presence of obesity, especially morbid obesity (BMI >35)
  • Diagnosis of type 2 diabetes mellitus
  • Diagnosis of metabolic syndrome
  • History of obstructive sleep apnea
  • Presence of insulin resistance
  • Chronic elevation of AST/ALT, otherwise unexplained.

Current Activities

We are studying CVC, an investigational product, intended for the treatment of patients with NASH with liver fibrosis.

We are sponsoring a fully enrolled Phase 2b study of CVC

CENTAUR demonstrated a clinically and statistically significant improvement in fibrosis of at least one stage without worsening of NASH after only one year of treatment. 

Topline results from the study were discussed on a conference call on August 9, 2016. The press release announcing the results can be found here.

External Resources

You can find more information about NASH on these websites:

American Liver Foundation

British Liver Trust