Liver Biopsy - Just Think About It
Emmet B. Keeffe, MD
Liver Biopsy: Indications, Contraindications, and
I'd like to convince you that we should do liver biopsy in
many patients but not all patients.
The historical role of liver biopsy was critical in the
diagnosis of all patients with acute and chronic liver
diseases. However, in our current practices the diagnosis of
chronic liver disease is now made by very sophisticated
virological, immunological, and genetic testing. For example,
we have serologic and virologic tests that diagnose hepatitis
A through E, we have antimitochondrial antibody (AMA) that
allows the easy diagnosis of primary biliary cirrhosis. We
have antinuclear antibody and smooth muscle antibody for
autoimmune hepatitis and we have both standard laboratory
studies and genetic tests to diagnose all of our genetic liver
Thus, today in our practice, liver biopsy is reserved
primarily for staging and in certain special situations like
in allograft dysfunction after transplantation or when we need
to analyze a specimen for iron or copper content.
I would now like to review the usual indications for a
liver biopsy. Firstly, to evaluate chronically elevated
aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) levels of uncertain cause; to confirm the diagnosis of
chronic liver disease, although as we'll see we can now
diagnose most liver diseases without the biopsy based on good
biochemical tests; to grade and stage chronic hepatitis, which
is the prime indication we use biopsy today; and to determine
the etiology of hepatic neoplasms when the imaging studies are
equivocal or uncertain.
We need to evaluate the response to treatment in certain
circumstances, such as autoimmune hepatitis or when we are
doing pharmaceutically funded clinical trials, and we need to
look at the outcome of a course of treatment. And then there
are special circumstances. We need to evaluate liver
transplant allograft dysfunction; to measure iron or copper in
certain circumstances; and rarely, to culture for organisms.
There are also less certain indications for liver biopsy.
One is to evaluate the cause of acute hepatitis. In acute
viral hepatitis the diagnosis is usually obvious based on
serologic and virologic tests. However, there are other
circumstances, for example, acute hepatitis as a presentation
of autoimmune hepatitis that requires a biopsy for
confirmation of diagnosis or sometimes in suspected acute
drug-induced hepatitis, a liver biopsy may be helpful.
In typical primary biliary cirrhosis (PBC) with an elevated
alpha phosphatase and a positive AMA, liver biopsy is less
often used than it had in the past. In typical primary
sclerosing cholangitis (PSC) with a diagnostic cholangiogram,
liver biopsy likewise is less often used. To stage PBC and PSC
is less important because therapy is relatively standard and
we will know when there's cirrhosis and a need for liver
transplantation. And finally, Budd-Chiari syndrome is
typically diagnosed by imaging studies and does not usually
require a biopsy.
Other less certain indications include a typical
hepatocellular carcinoma (HCC) or hepatic metastasis. We do
not want to biopsy certain focal lesions, such as a cavernous
hemangioma, and I would put forth, although it's a bit
controversial, that we probably do not want to biopsy all
patients who have nonalcoholic fatty liver disease (NAFLD)
particularly if we suspect there's only simple steatosis, and,
I do not think we need to biopsy all chronic hepatitis B (HBV)
and Hepatitis C (Hepatitis C Virus) patients.
I'd like to address the contraindications to liver biopsy
starting with the absolute contraindications. We cannot do a
liver biopsy if a patient is not cooperative. We must also
have satisfactory coagulation and the usual rules for impaired
coagulation that make liver biopsy a risk for bleeding such as
a prothrombin time (PT) of equal to or more than four seconds
over control, or an International Normalized Ratio (INR) equal
to or greater than 1.5, a platelet count according to
different rules less than 50,000 or less than 60,000, or a
bleeding time - although we do not do this routinely any
longer - of equal to 10 minutes or more. We don't want to do a
biopsy if we presume there's a vascular tumor such as a
hemangioma, echinococal disease, which does not come up very
often, or high-grade biliary obstruction from imaging studies.
Relative contraindications to a liver biopsy include
ascites, severe chronic lung disease, infections either in the
right pleural cavity or below the right diaphragm, amyloidosis,
myeloproliferative diseases, and hereditary hemorrhagic
telangiectasia. The latter 3 have been reported in some
studies to be associated with an increased tendency for
bleeding. Thus, these are relative and not absolute
I would now like to review the known complications of liver
biopsy, which we have to take in context of decisions in our
practice regarding performance of biopsy. First of all pain.
Pain occurs in .06% to 22% of patients in the literature.
Although in my own practice I must say, pain occurs routinely
in from 15% to 30% of the patients, and it may be pleuritic,
peritoneal, or diaphragmatic. Some patients may have a
vasovagal reaction with a faint. Hemorrhage is our most feared
complication which occurs in .2% to .3% and bleeding may be in
the peritoneal cavity (.03% to .7%), within the liver or in
the subcapsular space (.06% to 23%), or within the biliary
tree (.06% to .2%). And once in a while, in .001% to .4% of
the cases we may biopsy another organ. And the one we
particularly fear is the gallbladder although the lung,
kidney, and colon may also present problems if they are hit
rather than the liver (Reddy and Jeffers. Schiff's Diseases
of the Liver, 8th ed. 1999).
Other complications include bile peritonitis (.03% to .2%),
infectious problems including bacteremia, sepsis (.09%), or
abscess, pneumothorax or pleural effusion (.08% to .3%),
hemothorax (.2% to .5%), arteriovenous fistula (5.4%), and
reactions to the anesthetic agent (.03%) (Reddy and Jeffers. Schiff's
Diseases of the Liver, 8th ed. 1999).
Slide 1. Percutaneous Liver Biopsy Complications -- "Bottom
I've given you a laundry list of all of the complications
of liver biopsy. This is now the bottom line. This is what I
tell my patients as I approach them before a liver biopsy. You
can expect pain in 20% or 30% of biopsies, severe
complications occur in 3 per 1000 and the ones that we worry
about are hemorrhage or perforation of another organ, and a
death rate occurs with a frequency of about 3 per 10,000.