**3. Biopsy technique**

Performance of LB requires an adequate sized and dedicated space suitable for focused physician effort as well as safe patient recovery. There are different approaches for ob‐ taining liver tissue: percutaneous, transjugular, laparoscopic, and intraoperative, each having advantages and disadvantages. The biopsy technique is chosen on the basis of the indication, risks, and benefits in the individual patient. The most common approach for collecting a liver sample is percutaneous LB, either blinded or under US guidance. It is quick and safe procedures commonly performed by gastroenterologists or hepatolo‐ gists in out-patient settings.

A variety of needles are available for percutaneous LB; they are broadly classified into suc‐ tion needles (Menghini, Klatskin, Jamshidi), cutting needles (Vim-Silverman, Tru-cut), and spring-loaded cutting needles that have a triggering mechanism. The choice of a specific type of needle depends in part on local preference. Cutting needles usually produce a larger sample and are less likely to yield inadequate specimens than are suction needles, but they probably result in more complications [26], probably because the needle remains in the liver longer. Cutting needles can be useful in patients with cirrhosis. Suction needles are quicker (in the liver for a briefer time), easier to use, and less expensive, but tend to produce more fragmented samples. Disposable biopsy needles and biopsy guns are often used. A typical biopsy gun uses a modified 18-, 16-, or 14-gauge Tru-cut needle that is fired by a fast and powerful spring mechanism.

If the patient is not relaxed, a mild sedative should be administered just before the biopsy [27]. The current data on the use of prophylactic antibiotics is inconclusive. Prophylactic an‐ tibiotics have been recommended for patients at increased risk of endocarditis or with bili‐ ary sepsis [28]. However, recent results suggest that prophylactic administration of antibiotics following apercutaneous liver biopsy does not have a significant impact on the post-procedure results or incidence of infection [29]. During the procedure, patients placed in the supine position with the right hand resting behind the head [30]. For the blind ap‐ proach (also referred to as the percussion-palpation approach), caudal percussion is helpful in selecting the site for the biopsy over the hemithorax between the anterior and mid-axil‐ lary lines, until an intercostal space is reached where dullness is maximal at the end of expi‐ ration. The intercostal space below this point (usually in the 7th-8th intercostal space) is used. A local anesthetic, typically lidocaine (without adrenaline), is administered with a 25-gauge needle first subcutaneously and into the intercostal muscle and finally down to the dia‐ phragm and the capsule of the liver to reduce pain. The biopsy is performed while the pa‐ tient holds a breath in full expiration [31]. With a suction needle, aspiration is applied, and the needle is rapidly introduced perpendicularly to the skin into the liver and withdrawn quickly (within 1 second). This is the critical step in performing the biopsy to minimize the risk of lacerating the liver and inducing bleeding. If insufficient tissue is obtained on the first pass [32], a second pass is performed at a different angle. After the biopsy, the patients is usually kept on the right lateral decubitus position for up to 2 hours to reduce the risk of bleeding and the pulse and blood pressure are monitored. Post-procedure monitoring has evolved over time. Most complications manifest within the first few hours [26], and under certain circumstances more and more patients are being discharged just 1 or 2 hours after imaging-guided biopsy. Rightly, the recommended observation time after biopsy is between 2 to 4 hours. To direct the needle away from other organs and large vascular structures, physicians often use US guidance. The US has been used either throughout the entire proce‐ dure (real-time) or immediately before (site marking) through a technique in which the pa‐ tient subsequently has LB performed at the marked site. US guidance is the most controversial issue associated with LB [33-35]. Potential LB sites marked by percussion were changed in between 3 and 15% of patients after US was performed [36,37]. In an uncontrol‐ led Italian study, routine identification of the puncture site by US led to a diagnostic tissue sample in 99% of patients [35]. In diffuse liver disease, US marking or guidance has been associated with lower rates of pain, hypotension, and bleeding [31]. In a survey of 2084 liver biopsies in France, US guidance is used in 56% of cases (in 34% to determine the puncture site and in 22% to guide the biopsy) and is thought to reduce the frequency of severe com‐ plications [38]. Cost-effectiveness analyses have suggested that routine US guidance in clini‐ cal practice increases the cost of LB but may be cost-effective, with an incremental cost of \$2731 to avoid one major complication [39,40]. In addition, a large, randomized, prospective trial found that US use lowered the rate of post-biopsy hospitalization (most common rea‐ son for hospital admission was pain). Indeed there is a long track record of safety for per‐ forming percutaneous LB without imaging guidance. Thus, the role of US to guide percutaneous LB remains controversial. Use of ultrasound is not mandatory. A transjugular biopsy route offers a reasonable alternative to standard biopsy in high-risk patients (eg pres‐ ence of massive ascites, severe coagulopathy, morbid obesity with a difficult to identify flank site or fulminant hepatic failure) [41]. With transjugular LB, the liver tissue is obtained from within the vascular system, which minimizes the risk of bleeding [42,43]. The proce‐ dure is performed by interventional radiologists or hepatologists under X-ray videofluoro‐

hepatitis, which can lead to fibrosis and cirrhosis. LB is often considered if serum alanine aminotransferase (ALT) levels remain elevated after a modification of lifestyle and risk

**•** The need for LB in all patients with PBC and primary sclerosing cholangitis (PSC). In most cases the diagnosis can be established on the basis of a cholestatic pattern of liver chemistries and either anti-mitochondrial antibodies in PBC [6] or endoscopic retrograde cholangiopancreatography (ERCP) in PSC [23]; scoring systems based on quickly estab‐

lished clinical variables could be used to assess prognosis and response to therapy.

bed as late as 10 years after transplantation [24].

However, changes in management are often of minor importance [3].

**•** The need for protocol liver biopsies in all liver transplant recipients. A high rate of histo‐ logic abnormalities in the absence of liver biochemical test abnormalities has been descri‐

Overall, in patients without a definitive pre-biopsy diagnosis, LB has been shown to change the clinical diagnosis in 8% to 10% and to change the management in 12% of patients [25].

Performance of LB requires an adequate sized and dedicated space suitable for focused physician effort as well as safe patient recovery. There are different approaches for ob‐ taining liver tissue: percutaneous, transjugular, laparoscopic, and intraoperative, each having advantages and disadvantages. The biopsy technique is chosen on the basis of the indication, risks, and benefits in the individual patient. The most common approach for collecting a liver sample is percutaneous LB, either blinded or under US guidance. It is quick and safe procedures commonly performed by gastroenterologists or hepatolo‐

A variety of needles are available for percutaneous LB; they are broadly classified into suc‐ tion needles (Menghini, Klatskin, Jamshidi), cutting needles (Vim-Silverman, Tru-cut), and spring-loaded cutting needles that have a triggering mechanism. The choice of a specific type of needle depends in part on local preference. Cutting needles usually produce a larger sample and are less likely to yield inadequate specimens than are suction needles, but they probably result in more complications [26], probably because the needle remains in the liver longer. Cutting needles can be useful in patients with cirrhosis. Suction needles are quicker (in the liver for a briefer time), easier to use, and less expensive, but tend to produce more fragmented samples. Disposable biopsy needles and biopsy guns are often used. A typical biopsy gun uses a modified 18-, 16-, or 14-gauge Tru-cut needle that is fired by a fast and

If the patient is not relaxed, a mild sedative should be administered just before the biopsy [27]. The current data on the use of prophylactic antibiotics is inconclusive. Prophylactic an‐ tibiotics have been recommended for patients at increased risk of endocarditis or with bili‐ ary sepsis [28]. However, recent results suggest that prophylactic administration of

factors [22].

6 Liver Biopsy - Indications, Procedures, Results

**3. Biopsy technique**

gists in out-patient settings.

powerful spring mechanism.

scopy. Electrocardiographic monitoring is required to detect arrhythmias induced by passage of the catheter through the heart [41,44]. The patient is positioned supinely, with the head rotated opposite to that of the right internal jugular vein to be punctured, under local anesthesia using the Seldinger technique; then, a catheter is introduced into the hepatic vein under fluoroscopic control, and a needle biopsy of the liver performed through the catheter. Samples are retrieved from a Menghini or Tru-cut needle passed through the catheter into the liver. The transjugular approach permits concomitantly measurement of hepatic venous pressure gradient or opacification and imaging of the hepatic veins and inferior vena cava [45] helping in the diagnosis and management of select group of patients, particularly those with cirrhosis. In the past, a drawback of transjugular biopsy was the small and fragmented samples obtained. Better needles and more experience have led to improved quality of specimens. However, a transjugular LB is available only at a limited number of tertiary care facilities. Mortality is low (0.09%) [41], but perforation of the liver capsule can be fatal [46]. With laparoscopic approach, specific lesions can be identified and targeted precisely; thus it is especially useful in the diagnosis of peritoneal disease, the evaluation of ascites of un‐ known origin and abdominal mass, the staging of abdominal cancer. Laparoscopic LB is a safe procedure that can be performed under local anesthesia with conscious sedation, al‐ though it requires expertise that is not readily available. Absolute contraindications include severe cardiopulmonary failure, intestinal obstruction, bacterial peritonitis; relative contra‐ indications are severe coagulopathy, morbid obesity, and a large ventral hernia [33]. For most parenchymal liver diseases, the extra time and cost required for laparoscopy are not justified by the increased yield. Liver biopsies (needle or wedge) can also be obtained dur‐ ing abdominal surgery whenever liver disease is suspected. In many instances, an abnormal appearance of the liver during surgery for an unrelated procedure (most often cholecystec‐ tomy) is the first indication of an underlying liver disease. It is generally performed either with typical needle devices or by wedge resection by those with special expertise. While in‐ traoperatively obtained liver biopsies have the added advantage of obtaining adequate tis‐ sue sampling under direct vision from grossly visible/suspicious lesions, they are suboptimal for assessment of liver fibrosis and inflammation, due to preponderance of Glis‐ sen's capsule, wider portal tracts in the subcapsular area, and frequent but inconsequential surgically induced hepatitis. Other advantages are the ability to evaluate for potential extra‐ hepatic spread of malignancy and to look for a cause of unexplained ascites (peritoneal bi‐ opsy). The major disadvantages are cost and the added risk of anesthesia. Therefore, needle biopsy should be the technique of choice at laparotomy.

Absolute

Relative •Ascites •Morbid obesity

nous route.

be reliably predicted.

•Uncooperative patient

•Tendency to bleed

•History of unexplained bleeding



•Suspected hemangioma or other vascular tumor

**Table 2.** Contraindications to percutaneous LB

•Hydatid disease (Echinococcal cysts)

•Recent use of aspirin or other nonsteroidal anti-inflammatory drugs (within last 7-10 days)

Percutaneous LB with or without image guidance is appropriate only in cooperative pa‐ tients. As for any procedure, the patient that undergoes a LB should be able to understand and cooperate with the physician's instructions. An academic concern is that if the patient accidentally moves when the biopsy needle is in the liver, then a tear or laceration may oc‐ cur (which would in turn greatly increase the risk of bleeding). Thus uncooperative patients who require LB should undergo the procedure under general anesthesia or via the transve‐

Liver Biopsy: An Overview http://dx.doi.org/10.5772/52616 9

Coagulopathy is generally considered a contraindication to percutaneous LB, but the precise parameters that preclude LB are unsettled [47]. Generally, LB should be withdrawn when the prothrombin time (PT) is more than 3-4 seconds above the control value (International Normalized Ratio, INR>1.5) or when the platelet count is less than 60.000/mm3 [48]. Never‐ theless, it is important to emphasize that the relationship of abnormal indices of peripheral coagulation to the occurrence of bleeding after LB in patients with acute as well as chronic liver disease is uncertain, as limited data are available [47,49]. In patients with mild to mod‐ erate prolongation of PT, administration of fresh frozen plasma or appropriate clotting fac‐ tor concentrates may allow safe performance of a LB, as in hemophiliacs [50]. A low platelet count is probably less likely to result in bleeding in a cirrhotic patient with hypersplenism than in a leukemic patient with a comparable platelet count but platelet dysfunction. Proba‐ bly, platelet dysfunction due to aspirin use is a major risk factor as well. Whether patients with renal insufficiency are at increased risk of bleeding complications after LB is also un‐ certain [28]. In summary, the decision to perform LB in the setting of abnormal hemostasis parameters should continue to be reached as the result of local practice because there is no specific INR and/or platelet count cut-off at or above which potentially adverse bleeding can

•Infection in the right pleural cavity or below the right hemidiphragm

#### **4. Contraindications**

Although LB is often essential in the management of patients with liver disease, physicians and patients may find it to be a difficult undertaking because of the associated risks.

The consensus guidelines of contraindications for percutaneous LB are listed in Table 2.


#### **Table 2.** Contraindications to percutaneous LB

scopy. Electrocardiographic monitoring is required to detect arrhythmias induced by passage of the catheter through the heart [41,44]. The patient is positioned supinely, with the head rotated opposite to that of the right internal jugular vein to be punctured, under local anesthesia using the Seldinger technique; then, a catheter is introduced into the hepatic vein under fluoroscopic control, and a needle biopsy of the liver performed through the catheter. Samples are retrieved from a Menghini or Tru-cut needle passed through the catheter into the liver. The transjugular approach permits concomitantly measurement of hepatic venous pressure gradient or opacification and imaging of the hepatic veins and inferior vena cava [45] helping in the diagnosis and management of select group of patients, particularly those with cirrhosis. In the past, a drawback of transjugular biopsy was the small and fragmented samples obtained. Better needles and more experience have led to improved quality of specimens. However, a transjugular LB is available only at a limited number of tertiary care facilities. Mortality is low (0.09%) [41], but perforation of the liver capsule can be fatal [46]. With laparoscopic approach, specific lesions can be identified and targeted precisely; thus it is especially useful in the diagnosis of peritoneal disease, the evaluation of ascites of un‐ known origin and abdominal mass, the staging of abdominal cancer. Laparoscopic LB is a safe procedure that can be performed under local anesthesia with conscious sedation, al‐ though it requires expertise that is not readily available. Absolute contraindications include severe cardiopulmonary failure, intestinal obstruction, bacterial peritonitis; relative contra‐ indications are severe coagulopathy, morbid obesity, and a large ventral hernia [33]. For most parenchymal liver diseases, the extra time and cost required for laparoscopy are not justified by the increased yield. Liver biopsies (needle or wedge) can also be obtained dur‐ ing abdominal surgery whenever liver disease is suspected. In many instances, an abnormal appearance of the liver during surgery for an unrelated procedure (most often cholecystec‐ tomy) is the first indication of an underlying liver disease. It is generally performed either with typical needle devices or by wedge resection by those with special expertise. While in‐ traoperatively obtained liver biopsies have the added advantage of obtaining adequate tis‐ sue sampling under direct vision from grossly visible/suspicious lesions, they are suboptimal for assessment of liver fibrosis and inflammation, due to preponderance of Glis‐ sen's capsule, wider portal tracts in the subcapsular area, and frequent but inconsequential surgically induced hepatitis. Other advantages are the ability to evaluate for potential extra‐ hepatic spread of malignancy and to look for a cause of unexplained ascites (peritoneal bi‐ opsy). The major disadvantages are cost and the added risk of anesthesia. Therefore, needle

biopsy should be the technique of choice at laparotomy.

Although LB is often essential in the management of patients with liver disease, physicians

and patients may find it to be a difficult undertaking because of the associated risks.

The consensus guidelines of contraindications for percutaneous LB are listed in Table 2.

**4. Contraindications**

8 Liver Biopsy - Indications, Procedures, Results

Percutaneous LB with or without image guidance is appropriate only in cooperative pa‐ tients. As for any procedure, the patient that undergoes a LB should be able to understand and cooperate with the physician's instructions. An academic concern is that if the patient accidentally moves when the biopsy needle is in the liver, then a tear or laceration may oc‐ cur (which would in turn greatly increase the risk of bleeding). Thus uncooperative patients who require LB should undergo the procedure under general anesthesia or via the transve‐ nous route.

Coagulopathy is generally considered a contraindication to percutaneous LB, but the precise parameters that preclude LB are unsettled [47]. Generally, LB should be withdrawn when the prothrombin time (PT) is more than 3-4 seconds above the control value (International Normalized Ratio, INR>1.5) or when the platelet count is less than 60.000/mm3 [48]. Never‐ theless, it is important to emphasize that the relationship of abnormal indices of peripheral coagulation to the occurrence of bleeding after LB in patients with acute as well as chronic liver disease is uncertain, as limited data are available [47,49]. In patients with mild to mod‐ erate prolongation of PT, administration of fresh frozen plasma or appropriate clotting fac‐ tor concentrates may allow safe performance of a LB, as in hemophiliacs [50]. A low platelet count is probably less likely to result in bleeding in a cirrhotic patient with hypersplenism than in a leukemic patient with a comparable platelet count but platelet dysfunction. Proba‐ bly, platelet dysfunction due to aspirin use is a major risk factor as well. Whether patients with renal insufficiency are at increased risk of bleeding complications after LB is also un‐ certain [28]. In summary, the decision to perform LB in the setting of abnormal hemostasis parameters should continue to be reached as the result of local practice because there is no specific INR and/or platelet count cut-off at or above which potentially adverse bleeding can be reliably predicted.

A LB is precluded by tense ascites, because the liver will bounce away from the needle, thereby preventing adequate sampling of tissue, and the ascites will provide insufficient tamponade in case of bleeding. In patients with tense ascites requiring a LB, a transvenous approach is commonly recommended. Acceptable options include total paracentesis per‐ formed immediately prior to percutaneous biopsy or transvenous or laparoscopic biopsy.

about when to investigate with imaging and/or to hospitalize the patient for observation

Liver Biopsy: An Overview http://dx.doi.org/10.5772/52616 11

Transient hypotension, due to vasovagal reaction, can occur, particularly in patients who are

Major complications were defined as life threatening or those that required hospitalization, prolonged hospitalization or those that resulted in persistent or significant disability. Most serious complications occur within 24 hours of the procedure, and 60% happen within 2

The most common serious complication is bleeding because of transection of a vascular structure [26]; bleeding may occur in the absence of pain. Mild bleeding, defined as that suf‐ ficient to cause pain or reduced blood pressure or tachycardia, but not requiring interven‐ tion, occurs in about 1/500 biopsies [58]. Severe bleeding is defined clinically by a change in vital signs with imaging evidence of intraperitoneal bleeding. Such bleeding has been esti‐ mated to occur in between 1 in 2.500 to 1 in 10.000 biopsies after a percutaneous approach for diffuse liver disease [59]. Although very rare, clinically significant intraperitonealhemor‐ rhage is the most serious bleeding complication of percutaneous LB; it usually becomes ap‐ parent within the first 2-3 hours after the procedure [26]. Free intraperitoneal blood may result from laceration of the liver capsule caused by deep inspiration during the biopsy or may be related to a penetrating injury of a branch of the hepatic artery or portal vein. The likelihood of hemorrhage increased with older age, presence of cirrhosis or liver cancer, and number of passes (≥ 3) with the needle during biopsy. The relationship between LB compli‐ cations and the number of needle passes is well documented [51]. The frequency of compli‐ cations increased with the number of passes performed at a rate of 26.4%, with one pass vs.

hours; between 1% and 3% of patients require hospitalization [33].

due to pain should be made on a case-by-case basis.

•Haemorrhage (intraperitoneal, intrahepatic, haemothorax)

•Pain (biopsy site, right upper quadrant and right shoulder pain)

•Perforation of the gallbladder or of the bowel

•Biopsy of the right kidney or the pancreas •Intrahepatic arteriovenous fistula

•Transient hypotension (vasovagal response)

•Infection (bacterial sepsis, local abscess) •Intrahepatic and subcapsular hematoma

frightened or emotional.

**Table 3.** Complications of percutaneous liver biopsy

•Pneumothorax, haemothorax

MAJOR •Dearth

•Bile peritonitis

•Pneumoperitoneum

MINOR

•Hemobilia

Relative contraindication is morbid obesity; in this case, transjugular biopsy is a logical al‐ ternative.

A standard LB is probably contraindicated by extrahepatic biliary obstruction, bacterial cholangitis, and the risk of bleeding after LB appears to be increased in patients with a known hematologic malignancy involving the liver [28].

Although LB in patients with mass lesions is usually safe, biopsy of known vascular lesions (ie hepatic hemangioma) should generally be avoided [51]. Patients who require LB and who have a large vascular lesion identified on imaging should undergo the procedure using real-time image guidance. Biopsy of potentially malignant lesions should be undertaken with care because it is believed that tumour vessels are more likely to bleed [51] and it can be also associated with a risk of tumour spread [52,53].

Biopsy of infectious lesions is generally safe. In the past, the presence of an echinococcal cyst was considered a contraindication to LB, because of the possibility of disseminating cysts throughout the abdomen and the risk of anaphylaxis. However, with recent advances in treatment, echinococcal cysts can be aspirated safely under ultrasound guidance [54].
