eMedicine Specialties > Gastroenterology > Liver

Diagnostic Liver Biopsy

Author: Atif Zaman, MD, MPH, Associate Professor, Department of Gastroenterology and Hepatology, Department of Public Health and Preventive Medicine, Oregon Health and Science University
Coauthor(s): Kenneth Ingram, PAC, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University; Kenneth D Flora, MD, Adjunct Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University; Consulting Staff, Department of Gastroenterology, The Oregon Clinic
Contributor Information and Disclosures

Updated: Nov 18, 2009

Introduction

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.

Complications of liver biopsy are rare but potentially lethal. A thorough understanding of the indications, contraindications, techniques, and common complications and their management is imperative. Therefore, the remainder of this article will address these topics individually.

Indications for Liver Biopsy

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.

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,³ or alcoholic liver disease.

Regardless of the indication for the biopsy, identifying which information the procedure is anticipated to yield is important.

Contraindications to Liver Biopsy

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)
• Difficult body habitus (transjugular route preferred)
• Suspected hemangioma
• Suspected echinococcal infection
• Uncooperative patient

Liver Biopsy Technique

As previously mentioned, a variety of needle types is available for obtaining a liver biopsy specimen. Needles may be divided into 3 broad categories—suction 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.

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.

Ultrasonographic or CT scan guidance 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.^4,5,6

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).³ 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. 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.

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.

Pressure is applied to the site, followed by an adhesive bandage. The patient is rolled onto the right side 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.

Complications of Liver Biopsy

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.

• Pain (0.056-22%)
  • Pleuritic
  • Peritoneal
  • Diaphragmatic
• Hemorrhage
  • Intraperitoneal (0.03-0.7%)
  • Intrahepatic and/or subcapsular (0.059-23%)
  • 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%)

Keywords

diagnostic liver biopsy, biopsy, liver biopsy, liver biopsy procedure, liver biopsy needle, biopsies, liver disease, hepatic disease, liver fibrosis, hepatic biopsy, liver disease diagnosis, percutaneous suction needle liver biopsy, percutaneous liver biopsy

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