By Peter G. Traber, M.D. on March 24, 2016
You may have seen Newsweek’s recent article on the growing impact of NASH, NASH Is the 21st Century’s Looming Health Threat. It’s a great article that vividly demonstrates the heartbreak of a NASH diagnosis and the shame and uncertainty faced by many patients.
“I’m in this situation and not for lack of good diet and exercise,” says Sandra, whose father died of liver disease 30 years ago. “You can blame me if you like, but I’m doing what I’m supposed to do.”
“Unlike those who suffer from other serious illnesses, NASH patients have no colored wristband denoting awareness, no annual fundraising race, no built-in support network.”
This article has gotten me thinking about ethical issues surrounding treating NASH and fatty liver disease.
There was a hint in the Newsweek article of the debate over whether medical intervention in NASH is at some level a questionable endeavor, as it may make better sense for society to address the epidemic of obesity directly rather than try and deal with NASH. However, that argument doesn’t hold up under scrutiny, as nearly 50% of the U.S. population is overweight or obese by the standard definitions. If you refused to treat medical problems that arise due to, or are exacerbated by obesity that would mean you wouldn’t treat heart disease, diabetes, or osteoarthritis. Even cancer is closely related to obesity and diet. Additionally, as I will elaborate on in a future CEO Perspective, lean people can also suffer from NASH so it is a lot more complicated than just a fat liver.
I wrote recently about how fatty liver disease helped motivate me to lose weight. I believe that awareness and lifestyle changes, including weight loss and exercise, will always be the best ways for the medical community and healthcare in general to address the looming health crisis of fatty liver disease. A recent study showed that a 10% reduction of body mass resolved NASH in 90% of the patients in the study.
However, I also remain convinced that there will always be a need for direct drug intervention for NASH. Not everyone will respond to a regime of weight loss and increased exercise. NASH is a progressive disease, and the question becomes: At what stage do we resort to direct medical intervention rather than focusing on lifestyle changes?
There was a study published last year in Hepatology [1] that took patients with a biopsy-proven diagnosis of NASH and followed them for up to 33 years, with an average of 26 years. This study was done in Sweden, so it was easier to track patients for that length of time than it might be here in the U.S. The study showed that if a patient started with stage 1 or 2 disease (mild fibrosis), they had no increased risk of mortality in comparison to a reference group. Let me repeat: Fatty liver disease itself didn’t affect patient mortality at all when followed for up to 33 years! However, if a patient had advanced fibrosis — stage 3 and 4 disease — they had a 3.3 times increase in mortality over the reference population.
To me, this study suggests that it would questionable to undertake a broad pharmaceutical approach to managing early-stage NASH. While a certain percentage of people will progress to advanced-stage NASH, we currently have no way of predicting which patient is at risk for this. Is it worth treating all 30 million people in the US with NASH, exposing them to the expense of the medication and its inevitable side effects when the treatment is not likely to have any impact on their long-term morbidity or mortality?
In contrast, we know that those who have NASH with advanced liver fibrosis do have an increase in morbidity and mortality related to NASH, so the more desirable approach might be to have a noninvasive test that can distinguish early-stage NASH from late-stage NASH and a follow-up treatment with a drug proven to be efficacious for late-stage NASH.
Galectin Therapeutics is distinctive among the companies developing therapies for treatment of NASH because we are focused exclusively on treatment of late-stage NASH with advanced fibrosis and cirrhosis. We have done this for the medical reasoning outlined here and the fact that the preclinical efficacy of our drug GR-MD-02 has a differentiated profile from other drugs in development in that it both prevents and reverses liver fibrosis. I think the science, the medical decision making, and ultimately the market will bear out that this is the point of greatest need.
- Journal of Hepatology, Volume 62, Supplement 2, April 2015, Pages S362–S363
