The role of liver biopsy (LB), the traditional gold standard for assessing liver disease, continues to evolve [1-4]. Fewer biopsies are being done for diagnosis as noninvasive tests such as new imaging techniques and accurate serological tests can now be done instead in many cases [2-4]. Most biopsies are currently performed for parenchymal disease not to make specific diagnosis but to assess the liver damage (the degree of inflammation, fibrosis) or the response to therapy . In contrast to past when nearly all biopsies were done for diagnostic purpose, presently more than 50% are being done for staging versus 15% for diagnosing the parenchymal liver disease . In addition, biopsies are often done to help in guiding the management of hepatitis C and nonalcoholic steatohepatitis and to assess the response to therapy [2, 3]. The increased use of liver transplantation as standard treatment of end stage liver disease of diverse etiologies has led to more biopsies being performed to differentiate the cause of graft dysfunction and to assess the suitability of potential liver donors for transplantation [1-3]. The dramatic increase in obesity, diabetes, hyperlipidaemia and hypertension (the metabolic syndrome) in western societies and its accompanying fatty liver problems are requiring liver biopsy for histological assessment . Evaluation of liver histology remains very important as LB is reported to change the clinical diagnosis in 8-14%, management in 12-18% and frequency of liver test monitoring in 36% of cases . Hence the main indication are
chronic hepatitis- for grading, staging, establishing a therapeutic strategy and monitoring therapy,
unexplained abnormal liver function tests or hepatomegaly and
follow up of patients after liver transplantation.
However no liver biopsy is free of risk as it is an invasive procedure. Rational assessment of overall risk in LB however is hampered by the wide variation in the indication and its outcome reported in the existing literature.
2. Factors that may influence the risk of complication following liver biopsy
Several factors my influence the risk of complication following liver biopsy and are listed in table 1
Coagulation status / bleeding disorders
Certain pathologies (liver cirrhosis, amyloidosis, malignancy, renal failure)
Use of image guidance
Type of technique (percutaneous / transvenous)
Number of needle passes
Needle diameter (large needle)
Type of needle (cutting or Automatic)
There are however several conditions which are more definitely associated with enhanced risk of bleeding and therefore warrant additional caution. These include patients with factor V11 (FV11) or 1X (F1X) deficiency, von Willebrand’s disease, other hereditary bleeding disorders and those with sickle cell anaemia . Patients with known underlying coagulopathy requiring liver biopsy represents a challenge but liver biopsy can be performed in these patients with definitive factor replacement. Nonetheless the risk benefit ratio must be carefully considered on a case by case basis
2.1. Ultrasound guided LB
This has been done to reduce the risk of both minor and major complications by avoiding large intra-hepatic vessels and other structures in the vicinity (gall bladder, colon, lung) and by decreasing the passes to sample a good specimen [18-21]. Ultrasound (US) may influence in selecting the site of puncture as was noted in 15% of cases in one study . The main causes for the change in site were due to ascites or small liver. US guided liver biopsy is reported to be performed in 56% of cases in France and in 76% of cases in USA [20,21]. This could either be performed as US guided or US assisted LB. US guided LB is particularly reserved for small liver, interposition of colon or lung, focal liver lesion (Haemangioma or cysts) or in patients with increased risk of bleeding [19-21].
3. Post biopsy care and complications
Rate of complications vary in different case series and relate in part to operator experience although the most experienced clinician still will encounter complications [1-4]. The risk of major complications is listed in table 2. Intraoperative needle biopsy observation indicates that almost all patients have transient bleeding from the capsular puncture site [1,2]. Following outpatient LB the period of observation varies among different institution but usually does not exceed 6 hours [1-4]. Patients who have had uneventful single pass biopsy may be discharged after 3 hours observation and if patients require analgesia may need observation for at least 4 hours [2-4]. The majority of major complications requiring hospitalization have been shown in prospective observational series to occur within 3 hours of biopsy, although later complication can occasionally ensue [1-4].
|Pain at biopsy site or right shoulder|
(pleuritic, peritonel, diaphragmatic)
|-intrahepatic or subcapsular||0.59 -0.23|
|Pneumothorax and /or pleural effusion||0.08-0.28|
|Biopsy of adjacent organs||0.001-0.044|
|gall bladder||-0.034- 0.117|
|Reaction to anaesthetic agent||0.029|
|Breakage of needle||0.02- 0.059|
A decision about when to investigate with imaging and or to hospitalize the patient for observation due to pain should be made on a case by case basis [1-4]. When pain is severe enough to require hospitalization radiological evaluation is usually warranted. While some would prefer the use of ultrasound as an initial investigation due to the ease with which it can be performed, others would perform an abdominal CT with contrast to be more definitive [1-4] (figure 1).
Bleeding can manifest as haemoperitoneum(0.3 to 0.7%), intrahepatic haematoma(0.59 to 0.23%) or haemobilia(0.058- 0.2%) [28-30](figure 1). Bleeding into peritoneal cavity produces pain, hypotension or less frequently may be asymptomatic. Intrahepatic haemtoma occurs in 1 to 23% of cases and are localized to intrahepatic or subcapsular region [28,29]. Usually they are small and asymptomatic but larger haematomas may cause pain from stretching of the liver capsule, hypotension or a delayed decrease in haematocrit [28,29]. The incidence of haematoma after LB seems to be high after LB with larger needles . Conservative treatment of haematoma together with a close follow up by US is generally sufficient [1-2,36]. The least common of the haemorrhagic complications is haemobilia which presents with the classical triad of upper gastrointestinal bleeding, pain and jaundice [4,18,36]. It may appear acutely following simultaneous perforation of adjacent intrahepatic bile ducts and blood vessels or more commonly much later following the erosion of haematoma or psuedoaneurysm into a bile duct . This occurs typically 5 days following the biopsy . Haemobilia is a very rare event with a frequency of 0.0006 to 0.023% in large series [31,37,38]. If bile is checked routinely after LB, haemobilia may be detected in 10% of cases [31,37,38]. Large volume of haemobilia may cause acute pancreatitis, although this is a very rare event with only 5 cases being reported in the literature .
The risk of bleeding is influenced by several factors including bleeding disorders, advanced age, ascites, high number of passages, large needle size, blind technique and certain liver pathologies including liver cirrhosis, amyloidosis, malignancy and renal failure [1-4,28,31]. The factors that are also related to the risk of bleeding include arterial bleeding and operator experience. Whether cutting needle(eg Trucut and automated variants) have a different risk than aspiration needles(eg, Menghini or Jamshidi) is unknown although some retrospective data suggest that cutting needle may be associated with slightly greater risk . At particular risk for bleeding are patients with chronic renal failure, those with underlying coagulopathy due to congenital abnormalities in coagulation parameter (such as haemophilics) and those with cirrhosis who may have acquired abnormalities in coagulation parameter. Use of DDAVP immediately before liver biopsy (0.3ug/kg ) body weight in patients with renal failure undergoing invasive procedure is useful [40,41]. In patients on chronic renal replacement therapy, dialysis is often performed prior to liver biopsy [1,2]. Although platelet count less than 60,000/cmm, INR greater than 1.3 and bleeding time > 10 minutes are well known practical contraindication to percutaneous LB, bleeding from liver does not correlate with the indices of peripheral coagulation when these are mildly impaired thus making bleeding an unpredictable event [42,43]. The accurate prediction of bleeding based on coagulation indices is problematic as the available data suggest poor relationship between bleeding and common laboratory tests (such as platelets, PT-NR etc) [42,43]. As a result there is wide variation in “acceptable” prebiopsy coagulation parameter . Whether the use of prophylactic blood products alters the risk of bleeding is currently unknown [1-3]. Furthermore because of the conventional parameter of coagulation correlate poorly with risk of bleeding, recommendation regarding correction of coagulation indices is limited and tempered by the risk of blood product exposure [42,43].
Transvenous liver biopsy (typically with jugular approach) is often recommended in patients with known or suspected bleeding diathesis because it is commonly perceived to be safer . However a recent systematic review reported minor and major complication in 6.5% and 0.6% respectively among the 7649 patients who underwent transvenous biopsy and may be related to capsular piercing with subsequent haemorrhage . However as this study was retrospective, there may have been a selective bias (i.e. it is highly likely that patients suspected to be at risk of bleeding would have been preferred for transvenous rather than percutaneous biopsy).
A number of other complications have been reported after liver biopsy. These include pneumothorax, hemothorax, perforation of any of the several viscous organs, bile peritonitis, infection (bacteraemia. abscess, sepsis), haemobilia, intrahepatic arteriovenous fistula, neuralgia and rare complication such ventricular arrhythmias with transvenous biopsy [1-4].
3.2.1. Infective complications
Transient bacteraemia which has been reported in 5.8 to 13.5% of patients after LB, is in most cases harmless . Intrahepatic abscess, septicaemia and septic shock are much rare events occurring only in patients with biliary obstruction and cholangitis or when the colon is incidentally punctured . Infectious complication appear to be increased in post transplant patients who underwent choledochojejunostomy during liver transplantation . There is however no recommendations of prophylactic antibiotics in patients scheduled for LB except in those with valvular heart disease
3.2.2. Complications in the thorax
Haemothorax, pneumothorax, leakage of ascites in the pleural cavity, subcutaneous emphysema occur after injury of pleura or lung or right diaphragm [18,31,46]. Haemothorax can occur even in US assisted LB when the patient changes his position or takes a deep inspiration after the site of puncture was set, the cause of bleeding being an injury to a diaphragmatic vessel. Pneumothorax is critical to recognize immediately after biopsy in presence of reduced breath sounds and typical radiographic findings because it can lead to immediate catastrophic outcome if not promptly recognized and treated[18,31].
3.2.3. Puncture of other viscera
This occurs rarely (0.01 to0.1%) and involves usually gall bladder, colon, and right kidney. The incidence is significantly reduced when LB is performed under US guidance[49,48]. Bile peritonitis, formation of bilioma or bilious pleural effusion occur mainly in patients with biliary obstruction although they are reports of them occurring even in patients without biliary obstruction or when the gall bladder is incidentally punctured[48,49].
The most critical aspect of management of complications such as bleeding, pneumothorax and visceral perforation is to recognize that one these complications has occurred. Suspicion of a potential complication should be high when the patient complains of pain that is out of proportion to the clinical events that surrounded the biopsy and is associated with drop in blood pressure and tachycardia and is then confirmed by radiological investigation. All complications are supported by initial resuscitation. Bleeding is most often managed expectantly with placement of wide bore intravenous cannula, volume resuscitation and blood transfusion as necessary. Angiographic embolisation and surgery may be required in some of these patients with persistent bleeding. Pneumothorax may be self limiting but may require more aggressive intervention depending on the severity of symptoms. Visceral perforation is usually managed expectantly in most situations. Observation is all that may be required although occasionally surgical intervention may be needed in the case of gall bladder puncture with persistent bile leak or in case of secondary peritonitis
The person who performs the LB should be acutely aware of the multiple potential complications (including death) that may occur after liver biopsy and it is of outmost importance to discuss these appropriately with the patient’s beforehand (class 1. Level C evidence)
Percutaneous liver biopsy with or without image guidance is appropriate only in cooperative patients and this technique should not be utilized in uncooperative patients(claas 1 level C)
Uncooperative patients who require liver biopsy should undergo the procedure under general anaesthesia or via transvenous route(class 1 level C)
In patients with clinically evident ascites requiring a liver biopsy a transvenous approach is generally recommended although percutaneous biopsy (after removal of ascites) or laparoscopic biopsy are acceptable alternatives(class 1 level C)
Haematological abnormalities particularly low platelet count (levels less than 50,000-60,000/ml) should be dealt with platelet transfusion prior to the procedure. This applies for both percutaneous and transvenous approach
The use of prophylactic or rescue strategies such as plasma, fibrinolytic inhibitors or recombinant factors should be considered in specific situations although their effectiveness remains to be established.(class 11a, level C)
In patients with renal failure or on hemodialysis, desmopressin(DDAVP) may be considered, although its use is necessary in patients on stable dialysis regimen(class 11a, level B)
Patients on chronic haemodialysis should be well dialysed prior to liver biopsy and heparin should be avoided if at all possible(class 1, level C)
The indications for liver biopsy are evolving. While liver biopsy may play a major role in management of some of the hepatic disorders, it is not without risk. Mild pain following the procedure is not uncommon however persistent and severe pain should warrant further investigation to rule out significant intraperitoneal bleed. Liver biopsy performed under ultrasound guidance and premedication is reported to significantly reduce complications including pain. The risk of major bleeding post liver biopsy is low but is of serious consequence as it is the main cause of a rare event of death. Among the various factors that may influence complication risk, patients coagulation status and operator experience are of outmost importance. The coagulation status should be optimized to the extent possible with platelet and coagulation factor infusion and the use of DDAVP and haemodialysis in patients with renal failure. The most critical aspect of management of these complications is to be acutely aware of it and to promptly treat it.