**4. Risks, complications and post-procedural complaints of liver biopsies**

ings. As already mentioned, the transvenous approach is preferred in certain categories of patients as it is considered safer, even though several pooled analyses showed similar risks

Risks and Benefits of Liver Biopsy in Focal Liver Disease

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The singular major complication of liver biopsy, caused in turn by consecutive severe bleed‐ ing is patient death. No consistent data regarding post-procedural mortality exists in the lit‐ erature, the most commonly quoted rate being less or equal to 1 in 10 000 biopsies [16], and seems to be greater after biopsies of malignant liver masses compared to diffuse parenchy‐

Other complications of liver biopsies include the perforation of other viscous organs, bile peritonitis (major complication which can result in death), infections (especially in posttransplant patients due to immunosuppressive medication), hemobilia, pneumothorax (in‐ stantly recognized on radiographs, essentially to diagnose quickly due to high risk of death) or hemothorax. Correct usage of imaging methods both when choosing the biopsy site and for surveillance of the procedure minimizes many of these risks, especially those related to puncturing adjacent structures [16]. The risk of needle track seeding when puncturing liver

malignancies exists in 1 to 3% of all cases [32], as will be detailed below.

**5. Current recommendations regarding conditions that require liver**

The indications for liver biopsy were greatly reduced since the recent introduction of accu‐ rate non-invasive tests which can evaluate liver parenchyma with minimal or no patient trauma. The concept of liver biopsy may evolve even further, if in vivo direct histological methods such as pCLE will provide important additional data. It is most likely that the rec‐ ommendations for liver biopsy will suffer further changes in following years. A series of these advancements will be discussed separately within this chapter. Below, we will de‐ scribe some of the main indications for liver biopsy, either for diagnostic purposes or for

The recent outburst of viral hepatitis cases (especially as a result of the increasing number of newly diagnosed virus C infections) represents a major health burden worldwide. With al‐ most four million people being infected in the United States alone, and between 130 and 170 million worldwide, chronic hepatitis C virus (HCV) infections and more than double those figures for hepatitis B virus (HBV) infections, this ensemble of viral diseases currently repre‐

Nowadays, the role of liver histology in the positive diagnosis of chronic viral hepatitis has greatly diminished. However, it still plays a central role when assessing both activity and progression of the disease [8, 35]. Sampling issues arise when evaluating liver parenchyma affected by chronic hepatitis, as the quality of the obtained specimens can greatly influence

with standard percutaneous methods [10,16].

mal disease [6].

**biopsy**

evaluating and staging liver disease.

**5.1. Grading and staging of chronic viral hepatitis**

sent the main cause of liver-related morbidity [33, 34].

The main risks for a patient subjected to liver biopsy were already briefly discussed in the previous paragraphs. Their frequency and predisposition in certain patient groups are de‐ terminant factors for choosing one biopsy technique in favor of another. The risk of bleeding cannot be excluded with any instrument, and liver biopsy is not recommended in most cases of suspected primary liver cancers because of a needle track seeding of tumor cells. These however do not exclude liver biopsy as a last resort diagnostic tool, when imagistic or serum tests proved constantly inconclusive or do not converge to an outcome.

The most commonly occurring complication of percutaneous liver biopsy is pain, present in up to 84% of procedures and ranging from mild discomfort to severe pain [28]. It is usually located in the right upper quadrant and it is referred to the right shoulder, with various in‐ tensities and time of installment. Moderate to severe pain is present in fewer than 5% of all patients, and may be the sign of a more severe complication such as bleeding or the punc‐ turing of the gallbladder [16, 29]. Mechanisms that lead to pain after the biopsy maneuver are not fully understood, however it is likely to be caused by bile or blood extravasation with subsequent capsule swelling (the only liver component with sensitive nervous termina‐ tions) [30]. Another cause of upper abdominal pain is the traction of the falciform ligament after the puncture. Cervical pain, as well as pain in the right shoulder, may also be caused by the irritation of the phrenic nerve. Subcapsular hematoma may lead to respiratory pain and irritation of the pleura or peritoneum may lead to vagal stimulation and consecutive va‐ gal shock, manifested through bradycardia, severe hypotension, weak pulse and intense pain in the upper abdomen [1]. In some cases of extreme pain, hospitalization and further imaging tests are required to determine the correct course of action for these patients.

However, the most important complication of liver biopsy is bleeding. The most severe bleedings occur intraperitoneally, when they determine a drop in vital signs and can be vi‐ sualized through imaging [16, 31]. Urgent hospitalization and blood transfusion, even fol‐ lowed by surgery or radiological intervention may be required. Nevertheless, these cases are scarce, with 1 in 2 500 up to 10 000 biopsies incidence, while less severe cases which do not require blood transfusions or surgical maneuvers are more frequent, approximately 1 in 500 biopsies [16]. Serious bleeding-related complications usually occur within 2 hours of the procedure, and over 90% of all bleedings become evident within 24 hours of the procedure. Clinical symptoms are revelatory, as patients experience hypotension and shock. Age and the underlying conditions also are predictive factors, as older patients and liver masses are more frequently associated with post-puncture bleeding. A correlation between the needle type and the risk for bleeding was also cited in literature, as cutting needle seem to pose an increased risk compared to their suction counterparts [15]. Other factors are related to oper‐ ator experience, the diameter of the needles and their diameter [16].

A correlation between conventional coagulation tests and the risk of bleeding has not been sufficiently demonstrated until now; therefore no certain recommendations in this regard are currently in place [16]. The option to insert coagulation agents on the needle tract is con‐ sidered, especially in the US, with no definite data on its ability to prevent possible bleed‐ ings. As already mentioned, the transvenous approach is preferred in certain categories of patients as it is considered safer, even though several pooled analyses showed similar risks with standard percutaneous methods [10,16].

The singular major complication of liver biopsy, caused in turn by consecutive severe bleed‐ ing is patient death. No consistent data regarding post-procedural mortality exists in the lit‐ erature, the most commonly quoted rate being less or equal to 1 in 10 000 biopsies [16], and seems to be greater after biopsies of malignant liver masses compared to diffuse parenchy‐ mal disease [6].

Other complications of liver biopsies include the perforation of other viscous organs, bile peritonitis (major complication which can result in death), infections (especially in posttransplant patients due to immunosuppressive medication), hemobilia, pneumothorax (in‐ stantly recognized on radiographs, essentially to diagnose quickly due to high risk of death) or hemothorax. Correct usage of imaging methods both when choosing the biopsy site and for surveillance of the procedure minimizes many of these risks, especially those related to puncturing adjacent structures [16]. The risk of needle track seeding when puncturing liver malignancies exists in 1 to 3% of all cases [32], as will be detailed below.
