A doctor ordering a range
of blood tests, hoping to figure out what's causing a
patient to show signs of liver damage, might sound harmless enough - and
faster and more convenient than making the patient get more blood tests later.
But ordering too many liver tests at the same time may lead to
needless worry, biopsies and costs, says a University of Michigan
researcher who has studied the issue from many angles.
‘Doctors should hold off on ordering blood tests for rare liver conditions until they rule out more common ones.’
He and colleagues take on the issue of "overtesting" for liver
conditions in new papers in the Journal of Hospital Medicine and the Journal of Hepatology
Both papers recommend that doctors should exclude common liver issues
before testing for the uncommon ones. They also say that the computer
systems doctors use to order liver tests should help them pause and make
It's not the initial $100 blood test for elevated liver enzymes that
Elliot Tapper worries about. It's the trend toward
"one-stop shopping" testing, often ordered with the single click of a
checkbox on a computer screen, that happens after that.
The new papers focus on the 1-2% of all hospital
patients who show very high levels of liver enzymes, and the 8% of clinic patients who have slightly high levels.
"Physicians are legitimately thinking they're doing the right thing
by ordering the full 'panel' of tests, being thorough and trying not to
miss anything. In the hospital, they may be doing what a consulting
liver specialist has suggested," says Tapper, a gastroenterologist who
treats liver diseases and does data-driven research on them.
"But they're not aware of, or thinking about, the ramifications," he
continues. "This can include false positives for rare diseases that can
cause the patient and their family anxiety, and lead to unnecessary
liver biopsies." He advocates for a "directed" approach to liver
testing, instead of the current habit of "undirected" testing.
In hospital patients, he says, directed testing means ordering tests
for the most common causes of sudden severe liver issues first. That
includes hepatitis B or C, or problems caused by gallstones, a drug
overdose or blockage of blood vessels feeding the liver, which need
immediate care. Only after those are ruled out should tests be done for
rare, dangerous autoimmune or genetic disorders that attack livers.
In outpatients, liver issues related to alcohol or obesity and
diabetes are most likely the cause of slightly elevated liver enzyme
levels, followed by Hepatitis B or C. So tests for these conditions,
including an ultrasound of the liver to look for non-alcoholic fatty
liver disease, should be used first. Then, doctors should take a
patient's broader symptoms and lifestyle into account before testing for
In either setting, if the patient discloses that they've been
drinking excessive amounts of alcohol or using intravenous drugs (which
can increase the risk of hepatitis B and C) or they say they've been
taking a drug or dietary supplement that can cause liver damage, then
the need to test for the rarer conditions falls sharply.
The initial tests for these rare conditions - Wilson disease,
hemochromatosis, autoimmune hepatitis primary biliary cholangitis - set
a low bar. That means many people who take them will get a false
positive, and need a biopsy to rule the condition in or out. That can
cause anxiety, pain, and in some cases worry about the genetic risk to
Over-testing in hospital patients
Tapper and his former Harvard Medical School colleague offer new
data on the issue of liver over-testing, and advice for hospital-based
physicians, in the new Journal of Hospital Medicine paper. It's part of a
series called "Things We Do For No Reason."
They looked at liver testing orders placed at a large
Harvard-affiliated hospital over a five-year period, in patients whose
initial blood test suggested they were suffering some sort of severe
acute liver injury.
Of the nearly 5,800 patients, 86% had their blood sent out
for specialized testing for a wide range of liver problems, including as
well as the relatively common hepatitis B and C viral infections.
Many patients also got same-day blood tests done in the hospital for
some of these conditions - even though most of them don't cause acute
liver damage, and starting treatment a day or two later won't harm the
patient. And many patients never got confirmatory tests for rare
Over-testing for liver issues also comes with a financial cost,
Tapper notes. For instance, three tests for conditions that don't cause
acute liver injury are performed often on hospital patients with
severely elevated liver enzymes.
Together, the blood tests cost less than $65. But if they're done on
every hospitalized patient with high levels, it could cost $40 million a
year. And because they're often sent to outside testing labs, the wait
for results may prolong a patient's hospital stay. Plus, they can lead
to biopsies costing more than $1,500 each.
Over-testing in outpatients
In addition to the hospital-based sample, Tapper and his colleagues
have also used data from the U.S. and Britain to make a model of liver
testing in the outpatient setting.
In the Journal of Hepatology
paper, Tapper and U-M
colleague Sameer Saini and their colleague Neil Sengupta of the University of Chicago, publish the results of a computer
model they created using data from 10,000 adults who had slightly
elevated liver enzyme levels in their initial blood test.
They found that a directed approach to liver testing would have
yielded fewer false positives and half the number of liver biopsies. And
slight changes to the pre-testing probability of any given condition -
based on the patient's history and symptoms - can affect the patient's
recommended course and potential costs greatly.
"The main message to all physicians with a patient with elevated
liver enzyme levels is, think about what could really hurt my patient
and what's common, and direct your testing in that way first," says
Tapper. "If you find out on day seven that it's actually a rare case of
Wilson disease, the delay of a few days won't have changed the treatment
plan, or harmed the patient. But the dollar cost, and personal cost,
can be much higher for those who receive false positives and unnecessary
biopsies. Patients just want to be told straight-up what they have and
what they should do."