EDITORIAL

EUS-guided liver biopsy: a procedure looking for an indication

Liver biopsy has been the major diagnostic test for liver required amount of liver tissue. One study, which used
disease for many years. The first liver aspirate is credited computer-generated modeling, suggested that a biopsy-
to Paul Ehrlich, in 1883, and the first percutaneous liver specimen length of 25 mm had a 25% error rate.12 This
biopsy was performed in 1923.1 Yet, it was not until sheds some doubt on the validity of liver biopsy when
Menghini2 reported his 1-second needle biopsy of the one considers that, even in the most experienced hands,
liver that the procedure became widely accepted. There only a sixth of liver biopsy specimens are longer than
are a number of limitations of percutaneous liver biopsy, 20 mm.13
including sampling error, interobserver and intraobserver Because of the cost, morbidity, and inherent sampling
variability, and the risk of rare but serious complications. limitations of liver biopsy, there has been a major interest
Liver biopsy has been performed by a number of in discovering new, noninvasive ways to stage liver fibrosis.
routes: percutaneous, transvenous, and surgical (both To this aim, there has been an explosion in the number of
laparoscopy and laparotomy), and now, in this issue of tests to assess the stage of liver fibrosis, including direct
Gastrointestinal Endoscopy, guided by EUS.3 The proce-
dure, regardless of the way it is performed, is expensive
and invasive, and there are some questions in relation to
its accuracy for staging liver fibrosis.
Although EUS-guided liver biopsy represents
The primary indication for liver biopsy has been for the
diagnosis of parenchymal diseases of the liver and the an interesting method of obtaining liver tissue,
diagnosis of liver mass lesions. However, with the availabil- we do not believe that it will replace percuta-
ity of accurate blood tests for virology, immunology, and neous liver biopsy, even with refinements in
genetic markers, liver biopsy for a diagnosis is now less technique.
common. The major use of biopsy today is to stage the de-
gree of fibrosis in patients in whom the etiology of liver
disease is already known.
Because the amount of liver tissue removed at percuta-
and indirect biomarkers, transient US elastography, and
neous biopsy only represents approximately 1/50,000 of
magnetic resonance (MR) elastography. These tests have
the total liver volume,4 the potential for sampling error
been shown to be useful in differentiating advanced fibro-
is obvious. Autopsy and laparoscopy series have estimated
sis and cirrhosis from earlier stages of fibrosis but less use-
that cirrhosis may be missed on a single blind percutane-
ful in distinguishing between the early stages. Many
ous liver biopsy in 10% to 30% of cases.5,6 A study that ex-
different biomarkers and panels of biomarkers have
amined laparoscopic liver biopsy of both left and right
been evaluated for the assessment of hepatic fibrosis.
lobes observed that cirrhosis was noted on one side but
No single serum biomarker has been shown to act as
not the other in 14.5% of cases and a difference of at least
a true surrogate marker of fibrosis as yet. A review of 14
1 stage between lobes was found in 33.1%.7 Sampling
studies of fibrosis markers in patients with chronic hepati-
error is influenced by the size and number of biopsy
tis C demonstrated that selection of arbitrary cutoff levels
specimens taken.8 An adequate specimen should be at least
can rule in or rule out fibrosis in 35% of patients. These
15-mm long and contain at least 5 portal tracts.9,10 Most
panels of biomarkers were not shown to reliably differen-
percutaneous biopsy specimens are taken with 16-gauge
tiate between stages of fibrosis.14 Transient US elastogra-
to 18-gauge needles. An adequate biopsy specimen size is
phy (Fibroscan; Echosens, Paris, France) is a novel
extremely important in the assessment of fibrosis because
technique that relies on an increase in liver stiffness,
of chronic viral hepatitis, one of the most common indica-
which is seen in advancing stages of hepatic fibrosis. It is
tions for liver biopsy today.11 Even these recommenda-
a very useful test in distinguishing advanced fibrosis
tions on the size of liver biopsy may underestimate the
(METAVIR F3–F4) from earlier stages (F0–F2). The sensi-
tivity for diagnosing cirrhosis is 87% and specificity is
Copyright ª 2009 by the American Society for Gastrointestinal Endoscopy
91%.15 In addition, excellent accuracy has been demon-
0016-5107/$36.00 strated in the diagnosis of earlier stages of fibrosis but,
doi:10.1016/j.gie.2008.11.031 again, not in distinguishing between the actual stages.16

www.giejournal.org Volume 69, No. 3 : Part 1 of 2 : 2009 GASTROINTESTINAL ENDOSCOPY 543

Editorial
Fibroscan has the advantages of being noninvasive, inex-
pensive, easily performed, reproducible, and acceptable
to the patient. In addition, sampling error may be reduced
compared with liver biopsy, irrespective of route, because
the volume of liver assessed is approximately 100 times
that of liver biopsy. MR elastography is a modification of
MR imaging sequences by using a dedicated probe that
can simply be added to the standard protocols used for as-
sessment of liver or biliary lesions and appears to be accu-
rate in distinguishing early from advanced fibrosis.17
In this issue of Gastrointestinal Endoscopy, DeWitt et al3
describe EUS-guided Tru-cut biopsy (EUS-TCB) in 21
patients with benign liver disease. This procedure has
been used for biopsy of various intra-abdominal organs
and EUS-guided FNA has been used to sample hepatic
malignancies. To our knowledge, this is the first reported
use of EUS-guided TCB in benign hepatic disease.
Although this represents an interesting method of obtain-
ing a liver biopsy, we do not think that it will replace
percutaneous liver biopsy, even with refinements in tech-
nique. The biopsy needle used was 19 gauge, compared
with 16 gauge to 18 gauge for most percutaneous biopsies.
In addition, the samples obtained were shorter than most at
percutaneous biopsy. Multiple passes were needed to ob-
tain an adequate total length of liver tissue (median 3
passes), and, yet, an overall sample length of 15 mm was
only obtained in 4 of 21 patients, with a median total sam-
ple length of 9 mm in the 21 patients. It is known that per-
forming multiple passes increases the risk of complications
with percutaneous liver biopsy,18,19 and this will probably
be the case with EUS-TCB. Of the biopsy specimens, 29%
were less than 3 mm in length, a size that would be un-
likely to yield any useful information. The samples also
only had a median of 2 complete portal tracts, because
of both the short samples and the narrow diameter of
the needle. Only 6 of 21 or 29% of samples had 6 or
more portal tracts.
The investigators report that a histologic diagnosis was
obtained in 90% of the biopsy specimens but was suffi-
cient to provide clinical diagnostic information in 71%. Al-
though a histologic diagnosis may have been made in 90%,
doubt would have to be raised regarding confidence in
the diagnosis in view of the small samples. It is particularly
important to highlight that, in the 4 patients in whom the
biopsy was performed for suspected cirrhosis, none of the
samples were deemed sufficient to exclude cirrhosis. This
finding must be critically examined in light of the 70% to
90% accuracy of percutaneous liver biopsy and sensitivity
of more than 80% when using Fibroscan in the diagnosis
of cirrhosis. The diagnosis of cirrhosis is extremely impor-
tant in view of the risks of developing portal hypertension
and hepatocellular carcinoma. The advantages of screen-
ing for these complications of cirrhosis are now well estab-
lished to institute prophylactic treatment against variceal
bleeding and early treatment of hepatocellular carci-
noma.20-22
544 GASTROINTESTINAL ENDOSCOPY Volume 69, No. 3 : Part 1 of 2 : 2009
Manning & Afdhal
Furthermore, the technique could not be considered an
alternative to transjugular liver biopsy, because patients
undergoing transjugular biopsy generally have thrombocyto-
penia, coagulopathy, or ascites. The specimens yielded by the
technique would be considered inadequate by most
experienced pathologists and do not meet any of the gener-
ally accepted criteria for adequacy of biopsy. In addition,
only the left and caudate lobes can be sampled with this
technique. There were no significant complications with
EUS-TCB, but this may be partly explained by patient selec-
tion. The patients were all outpatients, without evidence of
portal hypertension on imaging. The platelet count was
O150,000/mL (normal 150,000-450,000/mL) and interna-
tional normalized ratio %1.2 (0.9-1.1), and none of the pa-
tients had previous liver surgery. This group of patients
represents a group at an extremely low risk of complica-
tions. It is difficult to imagine that the complication rate
from this procedure would be any different than percu-
taneous biopsy overall, with the possible exception of
pneumothorax.
Although the current methods of performing liver bi-
opsy are expensive, performing the procedure by EUS
will only increase the costs associated with the procedure.
Even if the procedure were restricted to patients who
need a liver biopsy and who are undergoing EUS for an-
other reason, we believe that the inadequacy of the spec-
imens would lead to repeating the liver biopsy by another
route at a later date, which puts the patient at a higher risk
of complications. Although this procedure may be an al-
ternative to natural orifice transluminal endoscopic sur-
gery (NOTES) biopsy, as the investigators suggest, it is
not our opinion that NOTES biopsy is an acceptable
alternative to percutaneous liver biopsy. There have been
enormous advances in hepatology in recent years. Percu-
taneous liver biopsy remains an excellent method of ob-
taining liver tissue, albeit with the limitations outlined
above. Transjugular liver biopsy is an acceptable alterna-
tive in patients with a contraindication to percutaneous
biopsy. Although EUS-TCB appears very interesting, we
believe that the noninvasive assessment of liver fibrosis
is a more important goal than new ways of obtaining liver
tissue for histologic assessment.
DISCLOSURE
The following author disclosed financial relationships
relevant to this publication: N. H. Afdhal: EchoSens,
consultant, grant support from EchoSens and consul-
tant, research support from Quest Diagnostics. The other
author disclosed no financial relationships relevant to
this publication
Diarmuid S. Manning, MD
Harvard Medical School
Nezam H. Afdhal, MD
www.giejournal.org
Manning & Afdhal
Beth Israel Deaconess Medical Center
Harvard Medical School
Boston, Massachusetts, USA
Abbreviations: EUS-TCB, EUS-guided Tru-cut biopsy; MR, magnetic reso-
nance; NOTES, natural orifice transluminal endoscopic surgery; TCB,
Tru-cut biopsy.
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