10.1055/a-1978-6652Liver biopsy remains the gold standard for diagnosis of parenchymal liver disease.
For decades, percutaneous liver biopsy (PLB) has been performed at bedside, based
on percussion of the right hepatic lobe. Considered the gold standard, PLB now frequently
employs image guidance, most commonly utilizing pre-biopsy ultrasound marking or real-time
guidance. Transjugular liver biopsy (TJLB), performed by interventional radiologists,
is ideal for patients with ascites, coagulopathy or obesity. In almost all cases,
TJLB also samples the right hepatic lobe via the right hepatic vein given the anatomic
access advantage.
EUS-guided liver biopsy (EUS-LB) has become an attractive option, particularly with
the emergence of endo-hepatology, which can allow for variceal screening/management,
elastography, direct portal pressure measurement, and liver biopsy in the same setting.
EUS needles have evolved over the last 15 years, from fine-needle aspiration to spring-loaded
biopsy to fine-needle biopsy (FNB). Current FNB needles with incorporated cutting
surfaces allow for reliable core tissue acquisition. In the realm of liver histology,
however, it is all dependent on the adequacy of the sample. The American Association
for the Study of Liver Diseases (AASLD) defines an adequate liver biopsy sample as
a 2- to 3-cm-long specimen containing at least 11 complete portal tracts (CPTs) [1]. This is concordant with the recommendation from the British Royal College of Pathology,
requiring at least 2-cm-long specimen and > 10 portal tracts [2]. Thus, EUS-LB needs to provide reliable samples to meet these standards.
In some institutions, EUS-LB has supplanted both PLB and TJLB as the preferred route
for tissue acquisition. Compared to PLB and TJLB, EUS-LB is comparable for specimen
adequacy and may be superior when bi-lobar samples are obtained [3]. Advantages of EUS-LB include decreased patient anxiety and increased patient satisfaction,
as it is performed under sedation. In addition, real-time imaging is applied with
Doppler analysis to avoid large blood vessels. The post-procedural monitoring time
is shorter (typically 1 hour), and there is less post-procedure pain and lower complications
rates compared to the other biopsy methods [4]. EUS-LB also provides the option for bi-lobar (right and left lobe) biopsies to
decrease sampling error, particularly when assessing for non-alcoholic fatty liver
disease (NAFLD), which can have a patchy distribution [5]. This is typically the current algorithm followed by most endosonographers: a single
biopsy from both the right and left hepatic lobe. The question at hand is whether
EUS-guided left lobe biopsies alone are adequate for diagnosis, as compared to right
hepatic lobe or bi-lobar biopsies.
In this issue of Endoscopy International Open, Mithun et al [6] present a pilot study assessing the safety and accuracy of left-lobe EUS-LB compared
to right-lobe and bi-lobar EUS-LB. Fifty patients underwent EUS-guided 22G FNB with
a Franseen-tip needle from both the right and left lobe of the liver. Three blinded
pathologists interpreted the specimens for adequacy and diagnosis. Biopsies were performed
using the ‘fanning’ technique, with a dry ‘slow-pull’ withdrawal of the stylet. The
median number of needle passes to achieve an aggregate specimen length of at least
2 cm was 2 for the left-lobe and 2.06 for the right-lobe. There was no significant
difference in aggregate specimen length (LL: 2.31 ± 0.57 cm; RL 2.28 ± 0.69 cm; P = 0.476), number of CPTs (LL: 11.84 ± 6.71; RL: 9.58 ± 7.14; P = 0.106), and percentage of adequate specimens defined as length ≥ 2 cm + CPTs ≥ 11
(LL: 84 %; RL 76 %, P = 0.3197) between left-lobe and right-lobe biopsies. There was strong pathology agreement
between left-lobe and right-lobe biopsies (κ = 0.830), left-lobe and bi-lobar biopsies
(κ = 0.878) and right-lobe and bi-lobar biopsies (κ = 0.903).
The endosonographers subjectively reported that right-lobe EUS-LB was more challenging
compared to the left lobe. With regard to adverse events, one (2 %) serious complication
of intraperitoneal bleeding requiring laparoscopy for hemostasis occurred in a patient
who underwent three needle passes for EUS-LB of the right lobe. One additional minor
intraprocedural bleed was reported following two needle passes to the right lobe that
resolved spontaneously. The authors conclude EUS-LB from the left lobe may be safer,
technically easier and sufficient to obtain a diagnosis compared to right-lobe or
bi-lobar biopsy.
There are several aspects of this study that require critique. First, a 22G FNB needle
was used for tissue acquisition. Currently, the preferred needle for EUS-LB is a 19G
FNB needle, which demonstrates superior specimen adequacy and less tissue fragmentation
compared to a 22G FNB needle or a 19G FNA needle [7]
[8]
[9]
[10]. Furthermore, the Franseen-tip appears to outperform the fork-tip in 19G FNB needle
designs [10]. Likely due to the smaller needle gauge in this study, the mean number of CPTs was
below the adequate level for right-lobe biopsy (9.58), and just at the adequate level
(11.84) for left-lobe biopsies, leading to a higher rate of inadequate and compromised
samples compared to 19G FNB studies. In addition, use of the smaller needle may have
led to a higher number of passes required to obtain an adequate aggregate specimen
length, resulting in the increased bleeding rate from right-lobe biopsies. The authors
admit that the study was conceptualized in 2019 and implemented in 2020, when literature
was not as definitive on the superiority of a 19G FNB needle. It is notable that the
diagnostic rate in the study is comparable to those utilizing 19G needles.
A dry ‘slow-pull’ biopsy technique was used in this study. More recent literature
suggests that a wet suction technique, where the stylet is removed and the needle
primed with heparinized saline, is preferrable [11]. This can decrease blood clotting within the needle, allowing better tissue recovery
and decreased fragmentation. The number of to and fro needle movements has also been
evaluated; three actuations outperform a single needle actuation in regard to specimen
adequacy, with a needle “throw” depth of at least 3 cm. However, two needle passes
are required to reliably meet pathology criteria for tissue adequacy [12].
We agree that performing EUS-LB from the right hepatic lobe can be more challenging,
and frankly, awkward at times. The echoendoscope is in a long position in the duodenal
bulb, and frequently requires external rotation to adequately visualize the right
lobe. EUS-LB from the left lobe is technically easier, as it is performed from the
proximal stomach with the echoendoscope in a short, straight position.
Interestingly, 60 patients actually underwent EUS for the purpose of liver biopsy
in this study. However, 10 patients (17 %) were not biopsied, and thus, were excluded
for various reasons: intervening ascites, intervening large collateral vessels, small
hepatic lobe, gallbladder in needle path, and failed duodenal intubation. This “failure
rate” seems to be an outlier among EUS-LB studies, but is a reason to have additional
indications for the endoscopic procedure, such as variceal screening/management, direct
portal pressure management, and/or pancreatico-biliary evaluation.
The optimal technique for obtaining a liver biopsy is ultimately decided by resource
availability and cost, as all three techniques (PLB, TJLB, EUS-LB) can obtain adequate
specimens. In a cost-neutral world with unlimited resources, we feel EUS-LB would
be the ideal technique given patient comfort, lower complication rate and ability
to sample both hepatic lobes if needed. Unfortunately, Utopia does not exist, so liver
biopsy technique will remain dependent upon local expertise and availability.
Regarding the optimal technique for EUS-LB, with current evidence, we feel it should
be tailored to the individual patient and indication. If being performed to assess
nonalcoholic fatty livery disease or nonalcoholic steatohepatitis, then likely bi-lobar
biopsies should be performed to decrease sampling error due to regional variation
[4]. For other indications, we suspect two biopsies from the left hepatic lobe would
be sufficient, although yet proven. A Franseen-tip 19G FNB needle utilizing wet suction
with at least 3 needle actuations appears to be optimal [10]
[11]
[12]. However, a modified one-pass, one actuation with a 7-cm “throw” yielded an adequate
sample in all cases [10]. Common sense opines that one pass may be safer than two.
Mithun et al. raise the interesting question of whether EUS-LB from the left lobe
alone suffices for diagnosis of parenchymal liver disease. Given limitations of this
study, the question still remains. The number of biopsies, the number of needle actuations,
and the needle “throw” depth are still worthy of study, to optimize technique for
specimen adequacy. With the field of endo-hepatology in full motion, the time is right
for a larger prospective multicenter study to address these questions, as EUS-LB is
here to stay.
