**2. Indications**

Historically, LB was applied almost exclusively as a diagnostic tool [1]. Nevertheless, as the result of natural history data and the introduction of many new therapies for patients with liver disease, histological assessment of the liver has now got on an important role in clinical management. Therefore, LB currently has three major indications: for diagnosis, for assess‐ ment of prognosis and/or to assist in the management of patient with known liver disease.

Other indications for LB include documentation of alcoholic liver disease and assessment of its severity; evaluation of otherwise unexplained fever, particularly in patients with Ac‐ quired Immune Deficiency Syndrome (AIDS); detection of underlying granulomatous liver disease. LB also provides important diagnostic information regarding drug-induced liver in‐ jury. Liver histology is appropriately considered in conjunction with clinical and laboratory data in case of hereditary disorders, eg hemochromatosis (quantitation of the level of iron), Wilson's disease (quantitation of the level of copper), and alpha-1 antitrypsin deficiency.

Liver Biopsy: An Overview http://dx.doi.org/10.5772/52616 5

Liver histology may also be useful in detection of infiltrative processes such as amyloidosis [7]. Moreover, liver histology is often helpful in the setting of acute liver failure (ALF) [8]. An additional main use of LB is in assessing disease severity, particularly fibrosis, which, as a precursor to cirrhosis, may predict the emergence of complications of portal hypertension

Owing to the wide use and superior resolution of cross-sectional imaging such as ultraso‐ nography (US), computed tomography, and magnetic resonance imaging, focal lesions are being detected more often. Fortunately, the same technologic advances allow us to confi‐ dently establish a diagnosis without biopsy in most cases. Nevertheless, sometimes a biopsy of a suspected neoplasm will help change management. In this case, careful consideration of biopsy technique is important, as neoplasms have a higher bleeding risk and the potential to seed other sites along the biopsy tract or in the abdominal cavity [9]. At present, most biop‐ sies currently performed for parenchymal disease are not to make a specific diagnosis but to assess liver damage, particularly in situations where (prognostic) information about fibrosis may guide consequent treatment. For example, histological analysis of the liver in patients with chronic HCV-induced liver disease gives information about the grading (inflammatory activity) and the staging (degree of fibrosis) that predict the course of disease; the treatment is often advocated for those with at least moderate to severe staging, but may be withheld when fibrosis is minimal or absent [10]. Liver histology is also generally used in disease monitoring of patients with AIH [11]. Monitoring the plasma cell score on LB may help pre‐ dict relapse when a physician is considering reducing or discontinuing immunosuppressive therapy [12]. For further information on the role of histological analysis in the management of individual liver diseases, is possible to see guidelines for HCV [10], HBV [13], hemochro‐

matosis [14], cholestatic liver diseases [15], AIH [11], and Wilson's disease [16].

Assessment of liver histology after orthotopic liver transplantation (OLT) is highly valuable to assess for allograft rejection and the presence and intensity of disease recurrence. Contro‐ versy persists regarding the precise indications for LB. Among these controversies are the

**•** The precise cut-off of serum aminotransferase levels that should prompt a LB: any persis‐ tent elevation, 1.5 times the upper normal limit, or 2 standard deviations above the mean

**•** The need for LB in patients presumed to have NAFLD. Whereas imaging studies are sen‐ sitive for detecting steatosis, they are relatively not sensitive and nonspecific for detecting inflammation and fibrosis. Only on liver histology can distinguish fatty liver from steato‐

[17,18]. Even the definition of the upper limit of normal is controversial [19-21].

and also liver-related morbidity and mortality.

following:


•Evaluation of effectiveness of therapies for liver diseases (*eg*, autoimmune hepatitis)

**Table 1.** Indications for liver biopsy

LB is performed to evaluate diffuse parenchymal or focal liver disease (see table 1). LB is mainly helpful in patients with diagnostic uncertainty(eg, in patients with atypical features). Available data show that liver histology will, in a proportion of patients, point to a specific diagnosis [2] and lead to a change in patient management [3,4]. LB has long been considered as an important diagnostic adjunct in the evaluation of otherwise unexplained abnormalities of liver biochemical tests. For example, LB may exclude serious liver disease or detect un‐ suspected non-alcoholic fatty liver disease (NAFLD) or intrahepatic sclerosing cholangitis after an otherwise negative biochemical, serologic and radiologic evaluation [3]. Needle LB for diagnosis remains important in cases of coexisting disorders such as steatosis and HCV [5] or an "overlap" syndrome of primary biliary cirrhosis (PBC) with autoimmune hepatitis (AIH) [6].

Other indications for LB include documentation of alcoholic liver disease and assessment of its severity; evaluation of otherwise unexplained fever, particularly in patients with Ac‐ quired Immune Deficiency Syndrome (AIDS); detection of underlying granulomatous liver disease. LB also provides important diagnostic information regarding drug-induced liver in‐ jury. Liver histology is appropriately considered in conjunction with clinical and laboratory data in case of hereditary disorders, eg hemochromatosis (quantitation of the level of iron), Wilson's disease (quantitation of the level of copper), and alpha-1 antitrypsin deficiency.

**2. Indications**

4 Liver Biopsy - Indications, Procedures, Results

Diagnosis


enzymes levels

(AIH) [6].

Historically, LB was applied almost exclusively as a diagnostic tool [1]. Nevertheless, as the result of natural history data and the introduction of many new therapies for patients with liver disease, histological assessment of the liver has now got on an important role in clinical management. Therefore, LB currently has three major indications: for diagnosis, for assess‐ ment of prognosis and/or to assist in the management of patient with known liver disease.


•Evaluation of fever of unknown origin or immunocompromised patients with hepatomegaly or elevated liver


LB is performed to evaluate diffuse parenchymal or focal liver disease (see table 1). LB is mainly helpful in patients with diagnostic uncertainty(eg, in patients with atypical features). Available data show that liver histology will, in a proportion of patients, point to a specific diagnosis [2] and lead to a change in patient management [3,4]. LB has long been considered as an important diagnostic adjunct in the evaluation of otherwise unexplained abnormalities of liver biochemical tests. For example, LB may exclude serious liver disease or detect un‐ suspected non-alcoholic fatty liver disease (NAFLD) or intrahepatic sclerosing cholangitis after an otherwise negative biochemical, serologic and radiologic evaluation [3]. Needle LB for diagnosis remains important in cases of coexisting disorders such as steatosis and HCV [5] or an "overlap" syndrome of primary biliary cirrhosis (PBC) with autoimmune hepatitis

•Evaluation of post-transplant patient with abnormal liver tests (rejection vs. infectious aetiology)

•Identification and staging of parenchymalandcholestatic liver diseases

•Evaluation of the type and extent of drug-induced liver injury

Management – Developing treatment plans based on histologic analysis

•Evaluation of effectiveness of therapies for liver diseases (*eg*, autoimmune hepatitis)

•Pre-treatment evaluation and staging of chronic hepatitis

•Diagnosis of multisystem infiltrative disorders

Prognosis - Staging of known liver disease •Evaluation of pre-transplant living-related donor

**Table 1.** Indications for liver biopsy

Liver histology may also be useful in detection of infiltrative processes such as amyloidosis [7]. Moreover, liver histology is often helpful in the setting of acute liver failure (ALF) [8].

An additional main use of LB is in assessing disease severity, particularly fibrosis, which, as a precursor to cirrhosis, may predict the emergence of complications of portal hypertension and also liver-related morbidity and mortality.

Owing to the wide use and superior resolution of cross-sectional imaging such as ultraso‐ nography (US), computed tomography, and magnetic resonance imaging, focal lesions are being detected more often. Fortunately, the same technologic advances allow us to confi‐ dently establish a diagnosis without biopsy in most cases. Nevertheless, sometimes a biopsy of a suspected neoplasm will help change management. In this case, careful consideration of biopsy technique is important, as neoplasms have a higher bleeding risk and the potential to seed other sites along the biopsy tract or in the abdominal cavity [9]. At present, most biop‐ sies currently performed for parenchymal disease are not to make a specific diagnosis but to assess liver damage, particularly in situations where (prognostic) information about fibrosis may guide consequent treatment. For example, histological analysis of the liver in patients with chronic HCV-induced liver disease gives information about the grading (inflammatory activity) and the staging (degree of fibrosis) that predict the course of disease; the treatment is often advocated for those with at least moderate to severe staging, but may be withheld when fibrosis is minimal or absent [10]. Liver histology is also generally used in disease monitoring of patients with AIH [11]. Monitoring the plasma cell score on LB may help pre‐ dict relapse when a physician is considering reducing or discontinuing immunosuppressive therapy [12]. For further information on the role of histological analysis in the management of individual liver diseases, is possible to see guidelines for HCV [10], HBV [13], hemochro‐ matosis [14], cholestatic liver diseases [15], AIH [11], and Wilson's disease [16].

Assessment of liver histology after orthotopic liver transplantation (OLT) is highly valuable to assess for allograft rejection and the presence and intensity of disease recurrence. Contro‐ versy persists regarding the precise indications for LB. Among these controversies are the following:


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 factors [22].

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‐

Liver Biopsy: An Overview http://dx.doi.org/10.5772/52616 7


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