The path to NASH: understanding the role of severe obesity in a complex, multi-system disease
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We often think a person’s transition from a healthy to a diseased state is binary. But that’s often not the case. In reality, the onset of a disease is not something that occurs overnight, and the majority lie on a continuum that is impacted by a multitude of factors. Some of these factors are in a patient’s control. Others are not.
This is the case in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), two of the most complex diseases that “live” on this proverbial continuum. The clinical onset of NAFLD — and ultimately NASH — is a complex process that is closely related to obesity, insulin resistance and impaired adipose tissue metabolism.
For example, the prevalence of NAFLD correlates with the increasing prevalence of obesity. Similar research has emerged in the NASH space: In a study analyzing patients who submitted to bariatric surgery, 70.4% of those patients had NASH. The data suggest that the worldwide prevalence of obesity among NAFLD and NASH patients is 51% and 81%, respectively, and in populations with obesity, NAFLD prevalence varies from 60% to 95%.
While it is clear that a major contributor on this NASH continuum is severe obesity, it poses its own set of challenges. NASH researchers and drug developers often struggle to communicate the role obesity plays in disease onset and progression in a way that is both kind and empathetic — and also scientifically accurate. That being said, however difficult it is to achieve this delicate balance, it is crucial in order to approach treatment holistically.
This is the challenge we face as a company working to therapeutically address a disease that is (in part) a result of lifestyle choices. There’s an associated stigma that gets placed on the individual, and many struggle with feeling responsible for developing a disease that is so heavily linked to obesity and a low-activity lifestyle.
The severe obesity that plagues most people with NASH comes with mobility challenges, and routine, day-to-day tasks often prove to be major hurdles for people with this disease. This fuels a downward spiral of anxiety, self-recrimination and doubt, and individuals will often face poor self-esteem fatigue and depression as a result. As a part of the biotech and healthcare communities, our goal here is to judge, help, educate and provide meaningful treatment options to the individuals who need them most.
For example, this includes educating people of the long-term risks associated with years of an excess of calories consumed relative to energy consumption. While we know that obesity can lead to a variety of diseases and ailments, the effects of a chronic excess of calories are not necessarily obvious to everyone. The reality is that NASH, diabetes, cardiovascular disease (and more) are all connected to a surfeit of calories over an extended period of time, and this excess ultimately drives disease progression.
What we need are open, compassionate conversations that enable individuals to explore where they are on this disease continuum and how to establish better, healthier lifestyle choices. It’s not about sitting in judgment or “fat shaming.” It’s about fully understanding how obesity and other factors can manifest in disease later down the road. While most disease progression lies on a continuum, this is particularly true for NASH.
Individuals should be helped to understand that obesity can be an avoidable — and reversible — precursor to the disease to ensure that they receive the best care possible. People either at risk for or living with NASH can improve their overall health if they are willing to take a more active role in managing their risk factors. This can include reducing calorie intake and increasing activity to reduce weight, but other variables with respect to their health must also be considered. For instance, individuals at risk for NASH are frequently prescribed a plethora of other medications such as high blood pressure medicines, diabetes drugs or statins, and anxiety and depression treatments for additional disorders associated with obesity.
Changing eating habits can impact drug activity in the body and may cause unforeseen complications that should be taken into consideration to ensure optimal care. That is why we cannot shy away from these conversations, even as we practice empathy and compassion.
NASH is a complex, multi-system disease, requiring patient care and therapeutics that address its multi-factorial nature. But treating NASH extends beyond its clinical profile – it goes back to this notion of the continuum. Clinicians, researchers and drug developers must examine the entire person, confronting both the physical and emotional tolls of NASH. The only way to do this is through open and honest conversations about the role of obesity in the disease. Only then can we begin to effectively help the people who face this diagnosis.
