Q&A: Why We Need to Focus on NAFLD, NASH

Now that hepatitis C virus (HCV) infection has become highly curable in the age of direct-acting antiviral (DAA) therapy, experts are shining a brighter light on other conditions affecting the liver, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

In fact, NAFLD—a condition caused by a buildup of fat in the liver¹-and NASH-a more severe form of NAFLD accompanied by inflammation and liver cell damage¹—are positioned to become the next big hepatological concerns within the next few years.

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The prevalence of both conditions has escalated globally at a concerning pace, largely due to increasing rates of obesity. The number of people affected by these conditions is only projected to increase in the near future.

With this in mind, Consultant360 discussed NAFLD and NASH further with Jagpreet Chhatwal, PhD, senior scientist at the Institute for Technology Assessment at Massachusetts General Hospital and assistant professor at Harvard Medical School in Boston, Massachusetts.

Dr Chhatwal gave us a few key takeaways on NAFLD and NASH: their increasing prevalence, causes, diagnosis, and current and future treatment options.

Consultant360: Why has a greater focus shifted towards NAFLD and especially NASH in recent times?

Jagpreet Chhatwal: With the growing obesity epidemic, the incidence and prevalence of NASH are increasing. As a result, an increasing number of people will develop end-stage liver disease and liver cancer in the near future. In fact, NASH is projected to become the leading indication for liver transplant in the United States by 2020.

Unfortunately, there are no effective treatments for NASH. Lifestyle interventions can reverse the course of the disease, but very few patients can incorporate lifestyle changes for a sustained period.

C360: What are some common misconceptions about NASH?

JC: NASH is a silent disease, and most patients are not aware that this is a serious liver disease. In addition, most primary care providers do not necessarily consider NASH when seeing patients with diabetes or obesity, despite the fact that the prevalence of NASH in these patients is very high. The reasons for this may include lack of awareness about the adverse outcomes of NASH or lack of effective treatments among those who receive a diagnosis.

C360: What are the most important factors clinicians should consider when identifying and treating these diseases?

JC: Diabetes and obesity are the two leading risk factors for NASH. In addition, early evidence suggests that family history of NASH could be a risk factor. Because of a lack of effective therapies, clinical practice does not emphasize the early detection of NASH.

Another challenge is that there is no perfect non-invasive test to detect NASH. While research is being conducted in this area, biopsy still remains the gold standard for detecting NASH.

C360: What are some currently available options for the diagnosis and treatment of NASH, and are there any promising treatments on the horizon?

JC: Current treatments include lifestyle interventions—such as diet, exercise, and/or behavioral change—control of the metabolic syndrome, and liver-directed pharmacotherapy. Weight loss can be highly effective for treating NASH, but very few patients can maintain weight loss in the long-term. Bariatric surgery is another option that can improve or completely resolve steatohepatitis and fibrosis; however, only a subset of NASH patients are eligible.

There is lot of excitement about potential pharmacological treatments for NASH that may become available soon. Several pharmacological treatments are in development— there could be as many as 50 clinical trials on NASH, with several of them in phases 2 and 3.

On the diagnostics side, biopsy remains the gold standard for diagnosis of NASH, but is invasive, painful and expensive. As a result, only a small fraction of NASH patients undergo liver biopsy. However, extensive research is being conducted to develop non-invasive tests that include imaging-based and blood-based biomarkers.

C360: What would you say are the biggest research needs when it comes to NAFLD and NASH?

JC: There are several research needs, but I would pick two main areas of future research. First, we need effective therapies for NASH. Even the drugs in development, though promising, are far from being ideal. We do not know how long will patients need to be on treatment and what the long-term outcomes will be.

Second, we need evidence-based guidelines for early detection of NASH in high-risk groups. Such guidelines should weigh the harms vs benefits of screening, and evaluate which screening modalities will work in which subgroup of patients.

—Christina Vogt

Reference:

1. Nonalcoholic fatty liver disease & NASH. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash. Accessed on October 10, 2018.