summarize this "When it comes to managing junior surgical residents, there is a sort
of unwritten rule that Hippocrates might have stated as follows: First, let them
do no harm. That rule was in full effect during my early months at Johns
Hopkins, in 2001, on the surgical oncology service. We were removing part
of a patient’s cancerous ascending colon, and one of my jobs was to “pre-op”
him, which was basically like a briefing/semi-interrogation the day before
surgery to be sure we knew everything that we needed to know about his
medical history.
I met with this patient and outlined the procedure he was about to
undergo, reminded him not to eat anything after 8 p.m., and asked him a
series of routine questions, including whether or not he smoked and how
much alcohol he drank. I had practiced asking this last one in a disarming,
seemingly offhand way, but I knew it was among the most important items on
my checklist. If we believed that a patient consumed significant amounts of
alcohol (typically more than four or five drinks per day), we had to make sure
that the anesthesiologists knew this, so they could administer specific drugs
during recovery, typically benzodiazepines such as Valium, in order to ward
off alcohol withdrawal. Otherwise, the patient could be at risk for delirium
tremens, or the DTs, a potentially fatal condition.
I was relieved when he told me that he drank minimally. One less thing to
worry about. The next day, I wheeled the patient into the OR and ran my
checklist of mundane intern-level stuff. It would take a few minutes for the
anesthesiologists to put him to sleep, after which I could place the Foley
catheter into his bladder, swab his skin with Betadine, place the surgical
drapes, and then step aside while the chief resident and attending surgeon
made the first incision. If I was lucky, I would get to assist with the opening
and closing of the abdomen. Otherwise, I was there to retract the liver,
holding it out of the way so the senior surgeons could have an unobstructed
view of the organ they needed to remove, which was sort of tucked in
underneath the liver.
As the surgery got under way, nothing seemed out of the ordinary. The
surgeons had to make their way through a bit of abdominal fat before they
could get to the peritoneal cavity, but nothing we didn’t see most days. There
is an incredible rush of anticipation one feels just before cutting through the
last of several membranes separating the outside world from the inner
abdominal cavity. One of the first things you see, as the incision grows, is the
tip of the liver, which I’ve always considered to be a really underappreciated
organ. The “cool kids” in medicine specialize in the brain or the heart, but the
liver is the body’s true workhorse—and also, it’s simply breathtaking to
behold. Normally, a healthy liver is a deep, dark purple color, with a gorgeous
silky-smooth texture. Hannibal Lecter was not too far off: it really does look
as if it might be delicious with some fava beans and a nice Chianti.
This patient’s liver appeared rather less appetizing as it emerged from
beneath the omental fat. Instead of a healthy, rich purple, it was mottled and
sort of orangish, with protruding nodules of yellow fat. It looked like foie gras
gone bad. The attending looked up at me sharply. “You said this guy was not
a drinker!” he barked.
Clearly, this man was a very heavy drinker; his liver showed all the signs
of it. And because I had failed to elicit that information, I had potentially
placed his life in danger.
But it turned out that I hadn’t made a mistake. When the patient awoke
after surgery, he confirmed that he rarely drank alcohol, if ever. In my
experience, patients confronting cancer surgery rarely lied about drinking or
anything else, especially when fessing up meant getting some Valium or even
better, a couple of beers with their hospital dinner. But he definitely had the
liver of an alcoholic, which struck everyone as odd.
This would happen numerous times during my residency. Every time, we
would scratch our heads. Little did we know that we were witnessing the
beginning, or perhaps the flowering, of a silent epidemic.
—
Five decades earlier, a surgeon in Topeka, Kansas, named Samuel Zelman
had encountered a similar situation: he was operating on a patient whom he
knew personally, because the man was an aide in the hospital where he
worked. He knew for a fact that the man did not drink any alcohol, so he was
surprised to find out that his liver was packed with fat, just like that of my
patient, decades later.
This man did, in fact, drink a lot—of Coca-Cola. Zelman knew that he
consumed a staggering quantity of soda, as many as twenty bottles (or more)
in a single day. These were the older, smaller Coke bottles, not the supersizes
we have now, but still, Zelman estimated that his patient was taking in an
extra 1,600 calories per day on top of his already ample meals. Among his
colleagues, Zelman noted, he was “distinguished for his appetite.”
His curiosity piqued, Zelman recruited nineteen other obese but
nonalcoholic subjects for a clinical study. He tested their blood and urine and
conducted liver biopsies on them, a serious procedure performed with a
serious needle. All of the subjects bore some sign or signs of impaired liver
function, in a way eerily similar to the well-known stages of liver damage
seen in alcoholics.
This syndrome was often noticed but little understood. It was typically
attributed to alcoholism or hepatitis. When it began to be seen in teenagers, in
the 1970s and 1980s, worried doctors warned of a hidden epidemic of
teenage binge drinking. But alcohol was not to blame. In 1980, a team at the
Mayo Clinic dubbed this “hitherto unnamed disease” nonalcoholic
steatohepatitis, or NASH. Since then, it has blossomed into a global plague.
More than one in four people on this planet have some degree of NASH or its
precursor, known as nonalcoholic fatty liver disease, or NAFLD, which is
what we had observed in our patient that day in the operating room.
NAFLD is highly correlated with both obesity and hyperlipidemia
(excessive cholesterol), yet it often flies under the radar, especially in its early
stages. Most patients are unaware that they have it—and so are their doctors,
because NAFLD and NASH have no obvious symptoms. The first signs
would generally show up only on a blood test for the liver enzyme alanine
aminotransferase (ALT for short). Rising levels of ALT are often the first
clue that something is wrong with the liver, although they could also be a
symptom of something else, such as a recent viral infection or a reaction to a
medication. But there are many people walking around whose physicians have
no idea that they are in the early stages of this disease, because their ALT
levels are still “normal.”
Next question: What is normal? According to Labcorp, a leading testing
company, the acceptable range for ALT is below 33 IU/L for women and
below 45 IU/L for men (although the ranges can vary from lab to lab). But
“normal” is not the same as “healthy.” The reference ranges for these tests are
based on current percentiles,
[*1] but as the population in general becomes less
healthy, the average may diverge from optimal levels. It’s similar to what has
happened with weight. In the late 1970s, the average American adult male
weighed 173 pounds. Now the average American man tips the scale at nearly
200 pounds. In the 1970s, a 200-pound man would have been considered
very overweight; today he is merely average. So you can see how in the
twenty-first century, “average” is not necessarily optimal.
With regard to ALT liver values, the American College of
Gastroenterology recently revised its guidelines to recommend clinical
evaluation for liver disease in men with ALT above 33 and women with ALT
above 25—significantly below the current “normal” ranges. Even that may not
be low enough: a 2002 study that excluded people who already had fatty liver
suggested upper limits of 30 for men, and 19 for women. So even if your liver
function tests land within the reference range, that does not imply that your
liver is actually healthy.
NAFLD and NASH are basically two stages of the same disease. NAFLD
is the first stage, caused by (in short) more fat entering the liver or being
produced there than exiting it. The next step down the metabolic gangplank is
NASH, which is basically NAFLD plus inflammation, similar to hepatitis but
without a viral infection. This inflammation causes scarring in the liver, but
again, there are no obvious symptoms. This may sound scary, but all is not yet
lost. Both NAFLD and NASH are still reversible. If you can somehow
remove the fat from the liver (most commonly via weight loss), the
inflammation will resolve, and liver function returns to normal. The liver is a
highly resilient organ, almost miraculously so. It may be the most regenerative
organ in the human body. When a healthy person donates a portion of their
liver, both donor and recipient end up with an almost full-sized, fully
functional liver within about eight weeks of the surgery, and the majority of
that growth takes place in just the first two weeks.
In other words, your liver can recover from fairly extensive damage, up to
and including partial removal. But if NASH is not kept in check or reversed,
the damage and the scarring may progress into cirrhosis. This happens in
about 11 percent of patients with NASH and is obviously far more serious. It
now begins to affect the cellular architecture of the organ, making it much
more difficult to reverse. A patient with cirrhosis is likely to die from various
complications of their failing liver unless they receive a liver transplant. In
2001, when we did the operation on the man with the fatty liver, NASH
officially accounted for just over 1 percent of liver transplants in the United
States; by 2025, NASH with cirrhosis is expected to be the leading indication
for liver transplantation."