Liver Biopsy

Although liver biopsy may be an essential part of patient management, it is an invasive procedure with a relatively high risk of complications. Prospective studies have shown that the histological findings after liver biopsy alter treatment in less than one third of cases, although histology may help to establish the diagnosis.¹

Percutaneous liver biopsy

• Transthoracic (Transparietal) and subcostal liver biopsy:
  • The borders of the liver are usually defined by percussion or visualised by ultrasound.
  • Guided biopsies are considered safer and more accurate.
• Plugged liver biopsy:
  • Has been advocated as an alternative method for obtaining liver tissue in patients with impaired coagulation where transjugular biopsy is not available.
  • Biopsy is taken with a Tru-cut needle in the conventional manner but only the obturator containing the specimen is removed leaving the outer cutting sheath within the liver substance.
  • A plastic cannula is then inserted down the sheath and gelatin is injected as the sheath is withdrawn.
  • The procedure is safe and well tolerated.²

Transvenous liver biopsy

• For patients with disturbance of clotting, percutaneous liver biopsy is usually avoided because of the risk of bleeding.
• Transjugular: the internal jugular vein is cannulated on the right side and into the hepatic veins and position checked by injection of contrast medium.
• Transfemoral: sometimes a transjugular approach is not possible and a transfemoral route may be used instead.

• Is often used for biopsying lesions found fortuitously at routine laparoscopic surgery.
• It has also been used in centres where access to transjugular liver biopsy is not available, for patients with abnormal clotting parameters, and also in patients who have a combination of a focal liver lesion and a coagulopathy where a histological diagnosis is essential in the management of that patient.

• Acute hepatitis:
  • Liver biopsy is usually not necessary.
  • In chronic viral hepatitis, histology is of value in assessing those patients who will benefit from treatment and their response to it.
• Hepatitis C viral infection:
  • The role of liver biopsy is uncertain.
  • Biopsy is at present the only reliable method of assessing the degree of fibrosis and exclusion of other causes for liver damage.
• Hepatitis B viral infection:
  • Liver biopsy will help identify other cause for liver disease and can be used for grading fibrosis and inflammation.
• Genetic haemochromatosis:
  • Liver biopsy is indicated to define or exclude the presence of cirrhosis, in those cases where biochemical and genetic testing do not give a clear diagnosis and where other causes of liver disease need to be excluded.
• Infections and pyrexia of unknown origin:
  • Occasionally, histology and culture of biopsy material can help in the diagnosis of infections such as tuberculosis.
• Primary biliary cirrhosis:
  • There is usually no need to do a liver biopsy to make the diagnosis of PBC.
  • The presence or absence of cirrhosis is of limited prognostic significance.
• Primary sclerosing cholangitis:
  • Liver histology may be needed to make the diagnosis of small duct PSC.
• Alcoholic liver disease:
  • Liver biopsy is helpful in determining the degree of liver damage, estimating the reversibility and defining other contributory factors.
  • Liver histology is needed to confirm alcoholic hepatitis since the clinical diagnosis is incorrect in up to 20%.
• Autoimmune hepatitis:
  • Liver biopsy is indicated both in the diagnosis and follow up of patients with autoimmune hepatitis.
• Non-alcoholic liver disease:
  • Currently, it is not possible to differentiate fatty liver from non-alcoholic steato-hepatitis (NASH) without liver histology.
  • NASH (rather than steatosis) is associated with progression to cirrhosis, and therefore those with NASH would require follow-up and treatment.
  • But this would have major implications on resources and there is no licensed treatment for NASH.
• Abnormal liver tests of unknown cause:
  • This must be taken in context of the clinical situation and other routine investigations.
  • In those without a specific diagnosis following imaging and serology, histology may be important in diagnosis and indication of specific management.³
• Focal liver lesions:
  • Usually unnecessary with modern imaging techniques.
  • Risk of seeding tumours down the biopsy track but the degree of risk is currently unknown.
  • Liver histology is helpful when the nature of the lesion is unknown after imaging.
• Following liver transplantation:
  • The use of liver biopsy after liver transplant is increasing.
  • Liver biopsy is useful in the diagnosis of invasive CMV infection and in assessing rejection and recurrent disease.
  • Liver histology is usually necessary to determine the cause of liver test abnormalities following liver transplantation.⁴

• Uncooperative patient: may require sedation with midazolam or even general anaesthesia if the potential benefits outweigh the risks.⁵
• Extrahepatic biliary obstruction: risks of biliary peritonitis, septicaemic shock and death. With current imaging techniques (ERCP and MRI cholangiography), liver biopsies should only be performed in the context of biliary obstruction when there is doubt about the diagnosis and the benefit to the patient outweighs the risk. Under these circumstances the transjugular approach is preferable.
• Bacterial cholangitis: risk of inducing peritonitis and septic shock after liver biopsy has made cholangitis a relative contraindication. However if a liver biopsy is performed when a biliary system is infected then culture of a piece of liver can give useful bacteriological information especially in the context of investigation of TB or a PUO. Bacteraemia after percutaneous biopsy of a normal liver occurs in up to 14 % of biopsies.
• Abnormal coagulation indices:
  • Prothrombin time: If the prothrombin time is less than 4 seconds prolonged then percutaneous biopsy can be safely undertaken. If the prothrombin time is 4- 6 seconds prolonged then a transfusion of fresh frozen plasma may bring the prothrombin time into the desired range. If the PT is >6 seconds prolonged then other biopsy methods should be tried.
  • Thrombocytopaenia: if the platelet count is > 60 000/mm3 then the biopsy can be safely performed. If the platelet count is 40 000 - 60 000/mm3 then platelet transfusion may increase the count enough for the biopsy to be performed safely by the percutaneous route. If however platelet transfusion does not increase or the platelet count is less than 40 000/mm3 then alternative biopsy methods can be tried. Drugs that affect platelet function (such as aspirin or clopidogrel) should be discontinued (where possible) at least two days before biopsy.
• Ascites: options include total paracentesis prior to performing the percutaneous biopsy, image-guided biopsy, transjugular liver biopsy, or laparoscopic biopsy.
• Cystic lesions: modern imaging techniques can often identify benign cystic lesions of the liver. Cystic lesions within the liver may communicate with several structures including the biliary tree and therefore run the risk of biliary peritonitis after biopsy.
• Amyloidosis: reports of severe haemorrhage after liver biopsy. If a diagnosis of amyloidosis had already been made or is strongly suspected then one would need a good indication for performing a percutaneous liver biopsy rather than for performing a more benign procedure such as a rectal biopsy.
• Obesity: it may be difficult to identify the liver by percussion. In this situation, the biopsy should be done under ultrasound guidance.

• All patients who are about to undergo a percutaneous liver biopsy should ideally have had some form of imaging of the liver. Where possible, the biopsies should be done under direct ultra-sound guidance.
• The patient's platelet count and prothrombin time should be checked.
• Informed consent must be obtained and the patient should also be able to understand and co-operate with instructions given by the person performing the liver biopsy.
• Prophylactic antibiotics should be given to patients with valvular heart disease or those at risk of bacteraemia.

• The overall mortality rate in the 3 months after liver biopsy has been reported to be as high as 0.33%.⁶ Most of these deaths are the result of hepatic malignancy and advanced liver failure and very few are due solely to the liver biopsy. The overall mortality rate also varies according to the centre in which the liver biopsies are being performed.
• The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage. It has also been suggested that patients who bleed significantly (fall of >2g/dL Hb or become haemodynamically unstable) should be considered for either laparotomy or therapeutic angiography.
• Other serious complications include puncture of the gallbladder followed by biliary peritonitis. Patients with suspected biliary peritonitis should have an early laparotomy.
• Puncture of other viscera occur infrequently with an incidence of between 0.01% and 0.1%. Puncture of lung, colon, kidney and gallbladder together with pneumothorax, pleural effusion, and subcutaneous emphysema are well-recognised but rarely require intervention.
• Common problems following percutaneous liver biopsy include:
  • Pain (may be severe).
  • Hypotension and vasovagal episodes
  • Subclinical bleeding (detected by ultrasound) occurs in as many as 23% of patients.
  • Haemobilia occurs in a 0.05% of patients and presents with biliary pain, jaundice and melaena. Arterial embolisation may rarely be required.
  • Other recognised complications include sepsis, reaction to the local anaesthetic, breakage of the biopsy needle and intrahepatic arteriovenous fistulae.
• Complications of transjugular liver biopsy include:
  • Neck haematoma
  • Puncture of the neck and/or intra-thoracic arteries
  • Transient Horner's syndrome
  • Transient dysphonia
  • Pneumothorax
  • Cardiac arrhythmias
  • Infection
  • Perforation of the liver capsule (which may be associated with haemorrhage)
  • Fistula from hepatic artery to either portal vein or biliary radicles