The medical society that guides the treatment of patients is the American Association for the Study of Liver Disease (AASLD) their annual meeting is this week and it is virtual with a lot of first time patient access.  This is the first time patients have been welcomed so if the state of the art of liver research interests you, here is a link. Join Us!

https://tlmdx.aasld.org/

I am particularly excited by an event that has generally gone unrecognized but it is tremendously important to the patient community. They just don't know it yet.

Madrigal Pharmaceuticals is a small drug developer. They have been quietly doing their work while the pharmaceutical giants get most of the attention.  They have been allowed by the FDA to conduct a phase 3 trial of their drug Resmetirom, called Maestro-NAFLD, without requiring a biopsy.

1 A PATIENT'S VIEW OF THE NASH JOURNEY

When asked to write an article about the patient perspective, it was easy to say yes. Now, looking at this page it is a daunting task. As a cirrhosis patient and Chief Executive Officer (CEO) of the Fatty Liver Foundation, a patient advocacy group, I have my own personal story. My journey from thinking, I was perfectly healthy to facing a terminal illness is common enough but it does not represent what one might describe as the “patient journey.” Through the foundation, we interact with thousands of patients so I hope to provide here a broader glimpse into life as lived by patients.

When we consider patients as a general case in the USA, we see a population that is unwittingly choosing to be ill more often as they age and to die younger and with more difficulty than they expect. Nonalcoholic steatohepatitis (NASH), a disease that was undefined until 1980, has become a leading killer of middle age and older adults. A leading precursor, nonalcoholic fatty liver disease (NAFLD), is steadily increasing in all age groups.

TO READ THE PUBLISHED ARTICLE CLICK HERE

THE PROBLEM: The real liver experts don’t offer effective diet advice

(click here for a pdf with all the science references)

Currently, the experts who treat liver disease, (the specialists of AASLD), do not officially recommend any specific diet for liver health. The reason is because there are not enough well-designed dietary clinical trials focused specifically on the liver to give the organ experts confidence to make official dietary recommendations. This creates a serious dilemma. As patients we don’t have that luxury. We must make choices. We must live every day making food decisions and hope that our diet is a healthy one even if the experts can’t help us. No wonder we see endless variety in dietary advice and “experts” of all persuasions.

OUR GOAL: Design a diet strategy that minimizes the liver workload

Comorbid conditions increase the risk of being infected with COVID.  We hear that all the time but what does it really mean? A study was just released that provides some very important insights. Here is a chart showing the odds ratio, that is a measure of the relative risk compared to a healthy person.  Look closely. This is important. Note that NASH is over 14.

Broadly, these are the elements of metabolic syndrome and fatty liver disease.

Through the Foundation, we interact with a lot of people in pain and going through very difficult fearful things. Stepping away from that part of life and thinking of the things that move us emotionally, if even for a brief time is of great value.

There are so many things to be moved by. Who isn't touched by a baby's laughter? Memories of better times and places have power. I enjoy seeing the rarity of mastery of something. Grace is power perfected. A fan or not, who could deny the artistry of Muhammad Ali in his prime? Do you remember watching Secretariat run? Simone Biles is a breathtaking gymnast. The duet from Lakme always bring tears to my eyes. You don't have to be a fan to appreciate how hard it is to do what Baryshnikov and Kennedy make effortless. Can you imagine what it is like to be able to compete in an Ironman Triathlon? The list is endless and very personal for each of us but worth reflecting on. What moves you?

I was jogging in a park near my home yesterday.  Actually, jogging may be too grand of a term. We have all seen mature folks jogging.  I secretly call it the old guy shuffle, but I say I go jogging.

I was doing well and I heard footsteps behind me.  No surprise, I get passed often so I stayed near the edge.  To my surprise a woman came along side me and bid me a cheery good morning. OK, nice friendly person, but she was WALKING!!!

To give me my due, she was a very fast walker but darn, I am jogging in my accustomed style.

I recently wrote about our concern that the FDA had reset the clock on OCA, obeticholic acid, which is the first potential treatment for advancing fibrosis due to NASH. The core of my objection is that it was done without patient input.  As patients, who face potential terminal illness with no therapies, the prospect of a breakthrough drug is of vital interest.

I hope to not be unfair to the FDA here as I have not seen the actual text of their notice to cancel the planned Adcom meeting and delay a decision on OCA. That said, my understanding is that they stated that based on the data the FDA has reviewed to date, the Agency has determined that the predicted benefit of OCA based on a surrogate histopathologic endpoint remains uncertain and does not sufficiently outweigh the potential risks to support accelerated approval for the treatment of patients with liver fibrosis due to NASH

Don't bother with this if you don't care about liver disease.

The FDA just punted on a decision about the Intercept drug obeticholic acid, or OCA.

It was anticipated that OCA would be the first drug therapy for advancing fibrosis due to NASH.  It was the first drug to meet the FDA defined surrogate endpoints, most importantly the reduction by one stage of fibrosis, in a phase 3 trial.

OCA had been given breakthrough drug status earlier as the first drug that provided benefit to fibrosis patients.

It is being reported that patients who have NAFLD are about twice as likely to have a more serious illness than patients who are obese but do not have NAFLD if infected with COVID.

NAFLD is more likely to result in serious symptoms than obesity without NAFLD. This distinction is important for proper risk stratification.

I know that when you read about the risk factors associated with COVID they rarely mention liver disease. There have been some early reports that essentially say that liver risk is limited.  In the early turmoil of a crisis like the COVID pandemic a lot of information is fragmented and based on very small samples.

A study has just been uploaded to a pre-release server which takes a much more effective look at the question of whether NAFLD should be considered to be a risk factor for hospitalization should you become infected. 

With a bit of time, even things like the COVID virus are accommodated by our fears and broader concerns bubble back up.  One of the challenges faced by a lot of people with serious chronic illness is that they are alone physically or emotionally.

As I think about these past weeks and staying at home I realize that I am so very fortunate. My wife Rosemary makes my days in isolation a joy rather than a burden but I see messages in our patient forums that break my heart from people who are literally dying deaths of despair.  If you are well enough, reach out to those you know who are lonely. Chronic illness is difficult enough without having to do it alone.

Click the picture below for a link to a bit of fun on the subject of introspection. Many of you are old enough to remember this but it may be meaningful to our younger folks as well. (The picture isn't related, I just like it)

We are reaching the end of the beginning of the COVID pandemic. As society tries to return to some kind of normal the challenge is how, as an individual, to manage being a part of society if you have a medical issue.

If we look at some recent data from New York the issue is very clear.

Clearly, about 96% of the deaths are people older than 45. We have to remember that anyone can get it, but while it is hazardous for mature adults, most younger people will be OK. What that actually means is that it takes about 40 years for a typical person to develop some kind of chronic illness which puts them at risk.

That is all very interesting, but as part of the "at risk" population how do we think about the near term future? There aren't many good models but it is probably wise to keep a perspective even in the face of horrific news every day.

We are getting past the peak of the COVID deaths and we have used the strategy of social distancing and shutdown to try to prevent our hospitals from being overwhelmed. We all understand the tragedy of death by virus but the figure of merit that drove decisions by the government was ultimately ventilator supply and ICU occupancy. It really was an exercise in statistics.

Before you get mad at me, this discussion is about how our society makes decisions in the face of crisis. If you are a patient, or someone who may die some day, the way the system works is important so stick with me here. The way these processes work, in the back rooms and basements where real policy is made, matter to your life and you should understand it.

It is a fair analogy to think of this pandemic as a war. It is an invasion by a force which is hazardous and for which we have no defense. You might think of New York City as similar to the sinking of the Arizona at Pearl Harbor. We respond to the emergency with a host of defenses as we try to understand what we face. Some things work, some don't, but that is the nature of crisis.

As I watch the COVID tragedy unfold in the language of death rates and cytokine storms I find that Tennyson's poem, The Charge of the Light Brigade, which speaks of courage under fire despite the failures of command, comes to mind.

Forward, the Light Brigade!
Was there a man dismay'd?
Not tho' the soldier knew
Some one had blunder'd:
Their's not to make reply,
Their's not to reason why,
Their's but to do and die:
Into the valley of Death
Rode the six hundred.

In the manner of all armies, the healthcare workers and all of those that support them join the battle because it is theirs to do. Those of us who are high risk targets of COVID or are "non-essential" can but be humbled by the courage that is the definition of that profession.

How serious is this bug really?

We still see people arguing that this epidemic is overhyped and that we should not be closing the country down to fight it. Do they have a point?

One advantage of socialized medicine is that you get a consolidated database. Data from the Intensive Care National Audit and Research Center in London offers some perspective on how COVID-19 compares to the flu.

A recent report compares 2249 recent COVID-19 patients, whose mean age at admission was 60 years, compared to 4759 patients with non-COVID-19 viral pneumonia, most of them caused by flu with an average age of 58, who were hospitalized over the three complete years 2017-2019.

The Kabuki theater reveal is nearly here. The poorly orchestrated government response to COVID-19 is being forced to throw off the kimono.  We have watched the ratcheting up of the warnings for several weeks now and the step by step escalation of responses.  It is just the way of it I guess.  The government knew this information in late January. We wait too long for proof and consensus before we will take a difficult step.

The first thing to understand is the epidemiological facts about the virus. The big number is we should plan for a health crisis about 10 times as big as the flu.  The knee jerk announcements you are seeing today are in recognition of the risk.

Did you know that 20,000,000 Americans don't know they have asymptomatic liver disease?

Did you know that disease called COVID-19 is caused by the virus SARS-CoV-2?

Did you know that COVID-19 or SARS-2 is more dangerous to society than SARS-1.0 which hit in 2003 and killed 9.6% of those infected?

Did you know that if you have advancing fatty liver disease without any symptoms your risk of death from SARS-2 is higher than average?

I have some concern about writing this.  When we face a crisis, panic and reactions driven by fear can do great harm.  I do not wish to contribute to that, however, as an advocate for people faced with chronic illness, such as liver disease, I feel compelled to inform my community about the details.

Terminal illness is a fate that awaits us all. We know not the pathways of our personal  journey only that we will take one of those paths in a time not of our choosing.

I live in the land of the chronically ill. It is that time between health and end stage disease. The Foundation's niche is fatty liver disease but chronic illnesses of many kinds are passengers on the same train.

I deal with the newly diagnosed who are frightened and confused. I scheme ways to hold the devil back with stalwart warriors who fight for life. I comfort those for whom the journey is too hard and who are dying a death of despair. I walk with people who are triumphant after they receive liver transplants. I see the length and breadth and depth of this disease and as a society I see that we manage it badly.