6/10/2014 Diagnostic Liver Biopsy

http://emedicine.medscape.com/article/1819437-overview 1/7
Diagnostic Liver Biopsy
Author: Kenneth Ingram, PAC; Chief Editor: Julian Katz, MD more...
Updated: Oct 7, 2013
Overview
Practiced since the late 19th century, liver biopsy remains the criterion standard in the evaluation of the etiology and
extent of disease of the liver. Paul Ehrlich performed a percutaneous liver biopsy in Germany in 1883. In the late
1950s, Menghini developed a 1-second aspiration technique, which led to wider use of the procedure and broadened
its applications.
Since Menghini, the evolution of liver biopsy has been extensive. At present, percutaneous biopsies are performed
primarily by specialists in gastroenterology/hepatology or by radiologists.
A variety of approaches may be utilized for obtaining a liver tissue specimen. These include a blind percutaneous
approach after percussion of the chest wall, biopsy under the guidance of ultrasonography or computed tomography
(CT) scanning, intravascular tissue sampling via the hepatic vein, and intra-abdominal biopsy at laparoscopy or
laparotomy.
[1]
The choice of one technique over another is based on availability, personal preference, and the clinical situation.
Likewise, various needles are available for use, depending on the approach and on physician experience.
Some controversy remains as to what constitutes an adequate liver biopsy for accurate evaluation. In general, a
sample of 1.5 cm in length that is 1.2-2 mm in diameter and contains at least 6-8 portal triads is considered
adequate. This represents approximately 1/50,000th of the adult liver. Some hepatologists have advocated for
samples of 4 cm of tissue to minimize sampling error, while others have found samples of 1 cm to produce minimal
interobserver variability.
[2]
Although liver biopsy is generally safe and is currently considered the criterion standard for the evaluation of hepatic
inflammation and fibrosis, sampling error, rare complications, and, occasionally, significant patient anxiety do occur.
These factors have led to keen interest in the development of noninvasive tests for hepatic fibrosis. Several
modalities of these tests are currently under investigation, and 2 serum tests are now commercially available in the
United States.
Although these tests hold promise for reducing the need for liver biopsy, most hepatologists feel that their clinical
usefulness is limited at this time. The currently available tests appear to perform well at the extreme ends of the
spectrum of chronic liver disease, but results vary considerably in the intermediate stages of disease frequently seen
in clinical practice. Lack of validation of these tests in the community settings where they would most likely be used
is also a potential shortcoming of the current testing methods.
Indications
Liver biopsy, in combination with history and physical examination data, is a powerful clinical tool for diagnosing and
treating liver disease. Indications for obtaining a biopsy specimen are listed in as follows. These are divided
according to the type of clinical question framed.
Evaluation of abnormal hepatic laboratory test results
Confirmation of diagnosis and prognostication
Suspected hepatic neoplasm
Diagnosis of cholestatic liver disease
Evaluation of infiltrative or granulomatous disease
Following a case of liver transplantation to evaluate and manage rejection
To evaluate unexplained jaundice or suspected drug reactions
The biopsy specimen may be used to identify or exclude possible etiologies for physical or laboratory abnormalities.
Although various disease states may present similarly, diagnostic histologic patterns exist when used in the context
of clinical presentation. For example, infiltration of the hepatic parenchyma by fat may exist in diseases due to
alcohol abuse, hepatitis C, diabetes, and/or obesity. For each disease state, histologic clues exist that distinguish
one from the other.
[3, 4, 5]
Liver biopsy plays little role in the determination of the organism responsible for systemic infection because blood
cultures generally are revealing. The notable exceptions are intrahepatic tuberculosis and Mycobacterium avium
complex (MAC).
Another indication for biopsy is the determination of the extent of histologic change present in a biopsy specimen.
This involves scoring systems for the degrees of inflammation and fibrosis noted by the pathologist. Many systems
exist for describing the microscopic findings, ranging from simplistic to complex. The majority of scoring systems
report the degree of inflammation as the grade of the disease and the amount of fibrosis as the stage. An example
here would be the finding of moderate inflammation (grade 3) in a specimen from a cirrhotic (stage 4) liver.
The third set of indications is the monitoring of the progression of disease or of treatment efficacy. For example, liver
biopsy specimens frequently are used to evaluate and treat rejection following liver transplantation. Repeated
biopsies are used less frequently to monitor progression of diseases such as primary biliary cirrhosis, chronic
hepatitis C,
[6]
or alcoholic liver disease.
Regardless of the indication for the biopsy, identifying which information the procedure is anticipated to yield is
important.
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Contraindications
Contraindications to percutaneous liver biopsy are relatively few, but identifying contraindications is important to
avoid the major complications associated with the procedure. Contraindications to liver biopsy include the following:
Increased prothrombin time, international normalized ratio (INR) greater than 1.6
Thrombocytopenia, platelet count less than 60,000
Ascites (transjugular route preferred)
[7]
Difficult body habitus (transjugular route preferred)
Suspected hemangioma
Suspected echinococcal infection
Uncooperative patient
Anesthesia
After the patient is positioned and draped, administer local anesthesia with 1% lidocaine in both superficial and deep
planes.
Equipment
As previously mentioned, various needle types are available for obtaining a liver biopsy specimen. Needles may be
divided into 3 broad categoriessuction needles (Jamshidi, Klatskin, and Menghini), cutting needles (Tru-cut and
Vim-Silverman), and spring-loaded cutting needles. Each needle type has proposed advantages and disadvantages.
Suction needles are thought to yield desirable sample size but may fragment cirrhotic livers. Conversely, cutting
needles do not fragment liver tissue but may deliver inadequate tissue samples. Spring-loaded needles are thought
to decrease the amount of time that the needle is in the liver but may increase patient discomfort due to the clicking
noise of the triggering mechanism. Needle selection is largely a result of physician preference and experience.
Positioning
Place the patient supine, remove pillows, and elevate the right arm behind the head. The legs and feet may be
angled to the left to further open the right intercostal spaces.
Technique
Percutaneous suction needle biopsy technique
Patient preparation prior to undertaking a liver biopsy is essential. Ideally, education should begin during an office
visit prior to the biopsy. Explain the procedure in sufficient detail, with careful attention to anxiety and pain
management issues. Discontinue aspirin 1 week prior to the procedure. Nonsteroidal anti-inflammatory drugs should
be stopped 3 days prior to the biopsy procedure. The patient may, or may not, be asked to complete an overnight
fast. Eating prior to the procedure allows for gallbladder contraction, reducing the risk of gallbladder puncture. An
empty stomach may decrease the likelihood of postprocedure nausea and vomiting, however. This is an important
consideration because many biopsies are preformed under light sedation. In most instances, the biopsy procedure is
undertaken on an outpatient basis, following the recommendations outlined below.
[1]
American College of Physicians practice guidelines for outpatient liver biopsies
The patient must remain within 30 minutes of the facility at which the biopsy was performed.
The patient must be accompanied by a reliable person the first night after the procedure.
The patient should have no contraindications or conditions that increase the risk associated with the
procedure.
The facility where the biopsy is performed should have an approved blood bank, laboratory, inpatient bed,
and personnel available to the patient for at least 6 hours postprocedure. (Note: Many centers routinely
observe patients for only 2-4 hours postbiopsy, and published data indicate that discharge following 1 hour of
observation does not appear to affect patient safety. If this results in a change in practice habits, it may
significantly lower costs associated with percutaneous liver biopsy.)
Hospitalization should accompany evidence of bleeding, bile leak, pneumothorax, or pain requiring more than
one analgesic dose.
On the day of the biopsy, review recent laboratory evaluation of prothrombin time and complete blood count,
including platelets. Explain the procedure to the patient and obtain informed consent.
Place the patient supine, remove pillows, and elevate the right arm behind the head. The legs and feet may be
angled to the left to further open the right intercostal spaces. Percuss the right trunk to the point of maximum
dullness during both inspiration and expiration. This frequently corresponds to a point along the midaxillary line at the
second or third intercostal space above the costal margin. Mark this location with a surgical pen or other method.
See the images below.
Percussion over the liver.
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Marking the biopsy site.
Ultrasonographic or CT scan guidance (see the image below) may be useful, particularly if obtaining a biopsy of a
particular region or mass within the liver is desired. Some have advocated that all biopsies be performed under
ultrasonographic guidance; however, whether this reduces procedure-related morbidity or is cost effective is
controversial.
[8, 9, 10, 11]
Ultrasonography of the liver.
In a retrospective study of 100 patients with chronic hepatitis C infection, Flemming et al investigated whether higher-
quality biopsy specimens for the grading and staging of hepatitis C could be obtained with the help of
ultrasonographic guidance (50 patients) or without it (50 patients).
[6]
The primary biopsy quality determination was
made by assessing the number of complete portal tracts that were identifiable in the slides. The specimen's total
length and degree of fragmentation provided secondary outcome measures.
The authors found that ultrasonographically guided biopsies yielded higher-quality specimens than did the other
biopsies, having a larger number of complete portal tracks (11.8 vs 7.4; P < 0.001), a greater length (24.4 mm vs
19.7 mm; P = 0.001), and less fragmentation (P = 0.016), as well as a higher overall histopathologic quality
assessment (P = 0.026). However, Flemming and colleagues did not find a significant difference between biopsies
performed under ultrasonographic guidance and those that were not with regard to how effectively they could be
used to grade and stage chronic hepatitis C virus infections.
Insertion of the biopsy needle
Once a suitable biopsy site has been identified, sterile technique is employed. Prepare the field with Betadine
solution and place sterile drapes (see the images below). Administer local anesthesia with 1% lidocaine in both
superficial and deep planes. Patients occasionally notice a pain described as burning or shooting in quality that
radiates either transversely or to the right shoulder region. This pain is thought to represent contact of the anesthetic
with the capsule of the liver.
Preparing the field.
Sterile drape application.
Once adequate anesthesia has been obtained, a small nick in the skin is made with a surgical blade to allow
introduction of the biopsy needle. The biopsy needle is introduced within close proximity to the upper aspect of the
lower rib to avoid the intercostal nerve and vasculature.
As the needle is introduced, a series of several successive "pops" may be felt. Small amounts of saline contained in
the syringe are flushed until resistance is encountered. The resistance is the liver edge; at this point, the needle is
withdrawn slightly and flushed again to remove debris. Suction is applied to the syringe, and the patient is asked to
expire and to hold his/her breath. This shrinks the lung field and minimizes the risk of perforating the gallbladder,
while bringing the liver against the thorax wall. The biopsy sample is obtained. See the image below.
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Biopsy needle inside the liver.
Pressure is applied to the site, followed by an adhesive bandage. The patient is rolled onto the right side (see the
image below) and instructed to remain in this position for 1 hour to help prevent bleeding or bile leakage. Vital signs
are obtained every 15 minutes for the first hour, every 30 minutes during the second hour, and then hourly until
discharge.
Patient lying on right side.
The video below depicts ultrasound-assisted liver biopsy.
Ultrasound-assisted percutaneous liver biopsy. Video courtesy of George Y Wu, MD, PhD.
Complications
Complications of liver biopsy occur rarely but potentially are lethal. Complications of percutaneous liver biopsy, listed
below, outlines those complications most commonly observed in clinical practice.
The majority (60%) of complications occur within the first 2 hours, and 96% occur during the first 24 hours following
the procedure. Approximately 2% of patients undergoing biopsy require hospitalization for the management of an
adverse event. Vasovagal episode and pain are the most common reasons for admission.
Pain occurs in approximately 30% of patients undergoing a liver biopsy. It often is described as a dull ache in the
right upper quadrant or shoulder and typically is relatively short in duration, lasting less than 2 hours. This pain often
responds to analgesics. Unrelenting, severe abdominal pain is alarming, possibly indicating a serious complication
such as intraperitoneal hemorrhage or biliary leak.
Bleeding comprises a second group of complications. Presentations include subcapsular or parenchymal hematoma,
hemobilia, or free intraperitoneal hemorrhage. Intrahepatic or subcapsular hematomas are the most common of the
bleeding complications and are noted on approximately 23% of ultrasound images obtained following biopsy. Such
findings often are incidental, without associated clinical symptoms. They occur at similar rates after either blind or
laparoscopy-guided modalities, but incidence may be influenced by needle type and imaging technique. Large
hematomas are a rare cause of biliary obstruction. Symptomatic hematomas should be imaged by ultrasound but
usually respond to conservative treatment with analgesics.
Hemobilia presents as biliary colic, gastrointestinal bleeding, and jaundice. It is a rare complication of biopsy; one
study of 68,276 biopsies reported 4 instances of hemobilia. Clinical presentation ranges from chronic anemia to rapid
exsanguination. Hemobilia typically develops later than other complications. The average time to onset of symptoms
is 5 days following the procedure, but onset may occur earlier. Conservative treatment often is sufficient. However, if
clinically significant hemobilia is present, angiography is the modality of choice because both diagnosis and
intervention can be accomplished with a single procedure.
Biliary peritonitis is another noteworthy complication, although rare. Severe abdominal pain and vasovagal
hypotension herald its occurrence. Analgesics and fluid management usually are sufficient, but persistence of the
condition may necessitate endoscopic retrograde cholangiopancreatography with stent placement.
Intraperitoneal hemorrhage is the most serious of the bleeding complications. It is an early occurrence, most often
observed during the first few hours following the procedure, although reports of this complication as long as 24 hours
postprocedure have been noted. Late hemorrhage is associated with a poor outcome. The overall rate of occurrence
of peritoneal hemorrhage in a large study was 0.32%. Factors associated with increased risk of free bleeding include
increased age, hepatic malignancy, multiple needle passes, and cirrhosis. Abdominal pain and persistent
hemodynamic instability, presenting as tachycardia and hypotension, are typical of significant bleeding. Early
diagnosis via ultrasonography is preferred. Treatment includes aggressive fluid management and blood and platelet
transfusion, if indicated. An angiographer and surgeon should be alerted early in the process to facilitate rapid
intervention if needed. Angiography with potential embolization is the preferred intervention.
Bacteremia, pneumothorax, and accidental biopsy of other organs are rare complications. Their frequencies are
outlined below.
Complications of percutaneous liver biopsy
[12]
Pain (0.056-22%)
Pleuritic
Peritoneal
Diaphragmatic
Hemorrhage
Intraperitoneal (0.03-0.7%)
Intrahepatic and/or subcapsular (0.059-23%)
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Hemobilia (0.059-0.2%)
Bile peritonitis (0.03-0.22%)
Bacteremia
Sepsis (0.088%) and abscess formation
Pneumothorax and/or pleural effusion (0.08-0.28%)
Hemothorax (0.18-0.49%)
Arteriovenous fistula (5.4%)
Subcutaneous emphysema (0.014%)
Anesthetic reaction (0.029%)
Needle break (0.02-0.059%)
Biopsy of other organs
Lung (0.001-0.014%)
Gallbladder (0.034-0.117%)
Kidney (0.096-0.029%)
Colon (0.0038-0.044%)
Mortality (0.0088-0.3%)
Contributor Information and Disclosures
Author
Kenneth Ingram, PAC Assistant Professor, Department of Medicine, Division of Gastroenterology and
Hepatology, Oregon Health and Science University School of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Atif Zaman, MD, MPH Associate Professor, Department of Gastroenterology and Hepatology, Department of
Public Health and Preventive Medicine, Oregon Health and Science University
Atif Zaman, MD, MPH is a member of the following medical societies: American Association for the Study of Liver
Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological
Association, American Society of Gastrointestinal Endoscopy, and Oregon Medical Association
Disclosure: Nothing to disclose.
Kenneth D Flora, MD Adjunct Associate Professor of Medicine, Division of Gastroenterology and Hepatology,
Oregon Health Sciences University School of Medicine; Consulting Staff, Department of Gastroenterology, The
Oregon Clinic
Kenneth D Flora, MD is a member of the following medical societies: American Association for the Study of Liver
Diseases, American College of Gastroenterology, and American Gastroenterological Association
Disclosure: Nothing to disclose.
Specialty Editor Board
Robert J Fingerote, MD, MSc, FRCPC Consultant, Clinical Evaluation Division, Biologic and Gene Therapies,
Directorate Health Canada; Consulting Staff, Department of Medicine, Division of Gastroenterology, York Central
Hospital, Ontario
Robert J Fingerote, MD, MSc, FRCPC is a member of the following medical societies: American Association for
the Study of Liver Diseases, American Gastroenterological Association, Canadian Medical Association, Ontario
Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Oscar S Brann, MD, FACP Associate Clinical Professor, Department of Medicine, University of California at San
Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological
Association
Disclosure: Nothing to disclose.
Alex J Mechaber, MD, FACP Senior Associate Dean for Undergraduate Medical Education, Associate Professor
of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American
College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.
Chief Editor
Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American
College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical
Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics,
American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.
Additional Contributors
Medscape Reference thanks George Y Wu, MD, PhD, Professor, Department of Medicine, Director, Hepatology
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Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine, for assistance
with the video contribution to this article.
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