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There are many causes of liver disease and it is sometimes difficult to diagnose and work out the best treatment using tests such as non-invasive imaging techniques or blood tests. The main reasons for a liver biopsy are to:
- Help clarify diagnosis.
- Determine severity of liver damage or grade of tumour.
- Help predict prognosis in a person with a known diagnosis.
- Inform treatment decisions.
- Monitor disease progression or response to treatment.
- Obtain liver tissue for non-histological assessment (eg, microbiology, biochemical).
- Support research.
Methods of liver biopsy
There are numerous methods for obtaining a liver biopsy, including:
Percutaneous liver biopsy
- Transthoracic (transparietal) and subcostal liver biopsy:
- The borders of the liver are usually visualised by ultrasound.
- Guided biopsies are considered safer and more accurate.
- They are usually directed by ultrasound or computer tomography.
- Plugged liver biopsy:
- This is an alternative method for obtaining liver tissue in patients with impaired coagulation where transjugular biopsy is not available.
- At the end of the procedure the puncture tract is closed with Gelfoam® slurry to reduce the risk of bleeding and bile leak.
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.
- A transjugular liver biopsy is a safe and well-tolerated technique.
- Transfemoral: sometimes a transjugular approach is not possible and a transfemoral route may be used instead.
Endoscopic ultrasound-guided liver biopsy (EUS-LB)
- EUS-LB provides high-resolution image of both lobes of the liver and a biopsy needle can be safely directed into the liver.
- EUS-LB produces specimens at least comparable to, and in some cases better than, percutaneous or transjugular biopsies.
- Widely separated liver regions can be easily sampled with this technique.
- The diagnostic yield of EUS-guided biopsies depends on site, size and characteristics of target tissues as well as technical and procedural factors (type of needle, biopsy technique and material processing).
Laparoscopic liver biopsy
- This is often used to biopsy 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.
- Histology is of value in assessing those patients who will benefit from treatment and their response to it.
- Hepatitis C viral infection:
- Biopsy is at present the only reliable method of assessing the degree of fibrosis and exclusion of other causes for liver damage.
- It may be used to provide an histological assessment of the severity of liver inflammation, potential progression of fibrosis and the presence or absence of cirrhosis (LFTs correlate poorly with both necro-inflammatory and fibrosis scores found on liver biopsy).
- Hepatitis B viral infection:
- Liver biopsy can help identify other causes 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 (PUO):
- Occasionally, histology and culture of biopsy material can help in the diagnosis of infections such as tuberculosis.
- Cirrhosis: although ultrasound-guided liver biopsy is the gold standard for diagnosis of liver cirrhosis, its invasiveness and sampling bias limit its use.
- Primary biliary cirrhosis:
- There is often no need to do a liver biopsy to make the diagnosis of primary biliary cirrhosis.
- 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 primary sclerosing cholangitis.
- Alcoholic liver disease:
- Liver biopsy can be helpful in determining the degree of liver damage, estimating the reversibility and defining other contributory factors.
- Autoimmune hepatitis:
- Liver biopsy is usually 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 steatohepatitis (NASH) without liver histology.
- Abnormal LFTs 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.
- Focal liver lesions:
- Usually unnecessary with modern imaging techniques.
- There is a 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.
- There is a broad spectrum of complications encountered in early and late period after transplantation and these contribute to significant morbidity and mortality. Distinguishing among these complications often requires interpretation of allograft biopsies.
- Liver biopsy is useful in the diagnosis of invasive cytomegalovirus infection and in assessing rejection and recurrent disease. Histology is the gold standard for the diagnosis of rejection.
- Liver histology may be necessary to determine the cause of liver test abnormalities following liver transplantation.
- Haematological parameters in many patients with liver disease are abnormal, with disturbance of both thrombolysis and coagulation. It is recommended that for non-lesional biopsies in patients with liver disease, a transvenous route should be used if the international normalised ratio (INR) is above 1.4. For percutaneous lesional biopsies, the INR should be below 2.0. There is no evidence that fresh frozen plasma is effective in reducing bleeding and is not recommended.
- Extrahepatic biliary obstruction: risks of biliary peritonitis, septicaemic shock and death. With current imaging techniques (specifically, magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography), liver biopsy should be done for biliary obstruction only when there is doubt about the diagnosis and the benefit to the patient outweighs the risk.
- Bacterial cholangitis: the risk of inducing peritonitis and septic shock after liver biopsy has made cholangitis a relative contraindication. Bacteraemia after percutaneous biopsy of a non-infected liver occurs in up to 14% of biopsies.
- Ascites: percutaneous biopsy of the liver in the presence of large volume ascites is considered a contraindication. However, if a liver biopsy is clinically indicated in a patient with large-volume ascites, an image-guided percutaneous biopsy following total paracentesis or a transjugular biopsy can be considered.
- Amyloidosis: if amyloidosis is strongly suspected, the diagnosis should be made by subcutaneous fat or rectal biopsy since most cases of amyloid are systemic. However, if suspicion is low and in hepatomegaly of uncertain aetiology, a liver biopsy can be justified. The transjugular route is recommended.
- Obesity: may be difficult to identify the liver by percussion. The biopsy should be done under ultrasound guidance and in many cases the transjugular route might be preferable.
- Pregnancy: liver histology is rarely required during pregnancy but may be helpful in the diagnosis of new onset liver abnormalities. The benefits of biopsy need to be balanced against the risks to the mother and baby.
- Focal lesions with a cystic element: these may communicate with several structures, including the biliary tree, increasing the risk of biliary peritonitis after biopsy. Diagnostic fine needle aspiration may be used to evaluate these lesions. The risk:benefit ratio will depend on the characteristics of the lesion.
- Uncooperative patient: patients may be unable to cooperate for a variety of reasons, including anxiety. For anxiety, sedation with midazolam can be considered, with no increased risk. General anaesthesia can be used when the risks are justified.
Liver biopsy complications
Risks of percutaneous liver biopsy include bleeding, organ perforation, sepsis and death.
Complications are uncommon but there may be some mild pain or discomfort in the area of the biopsy. In a small number of cases there is some minor bleeding that soon stops.
Bleeding occurs in up to 10% with major bleeding occurring in less than 2%. Risk factors for bleeding from percutaneous biopsy include older age, comorbidities, indication for biopsy and coagulation. There is little conclusive evidence that operator status and number of passes significantly affects the risk of bleeding.
On occasion it is possible for bile to leak from the liver internally. There is a small risk that the small wound will become infected after the biopsy.
Mortality associated with biopsy is less than 1 in 1000.
After a biopsy, patients should seek medical advice when:
- Bleeding occurs from the site of the biopsy.
- The biopsy site becomes red, angry looking or swollen.
- A high temperature (fever) develops.
- The biopsy site is still painful after a few days and painkillers do not help.
Further reading and references
Chowdhury AB, Mehta KJ; Liver biopsy for assessment of chronic liver diseases: a synopsis. Clin Exp Med. 2023 Jun23(2):273-285. doi: 10.1007/s10238-022-00799-z. Epub 2022 Feb 22.
Di Tommaso L, Spadaccini M, Donadon M, et al; Role of liver biopsy in hepatocellular carcinoma. World J Gastroenterol. 2019 Oct 2825(40):6041-6052. doi: 10.3748/wjg.v25.i40.6041.
Neuberger J, Patel J, Caldwell H, et al; Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology. Gut. 2020 Aug69(8):1382-1403. doi: 10.1136/gutjnl-2020-321299. Epub 2020 May 28.
Tsang WK, Luk WH, Lo A; Ultrasound-guided plugged percutaneous biopsy of solid organs in patients with bleeding tendencies. Hong Kong Med J. 2014 Apr20(2):107-12. doi: 10.12809/hkmj133972. Epub 2013 Jul 22.
Dohan A, Guerrache Y, Dautry R, et al; Major complications due to transjugular liver biopsy: Incidence, management and outcome. Diagn Interv Imaging. 2015 Jun96(6):571-7. doi: 10.1016/j.diii.2015.02.006. Epub 2015 Mar 12.
Pineda JJ, Diehl DL, Miao L, et al; EUS-guided liver biopsy provides diagnostic samples at least comparable with percutaneous or transjugular routes. Gastrointest Endosc. 2015 Aug 21. pii: S0016-5107(15)02797-2. doi: 10.1016/j.gie.2015.08.025.
Diehl DL, Johal AS, Khara HS, et al; Endoscopic ultrasound-guided liver biopsy: a multicenter experience. Endosc Int Open. 2015 Jun3(3):E210-5. doi: 10.1055/s-0034-1391412. Epub 2015 Feb 27.
Yeom SK, Lee CH, Cha SH, et al; Prediction of liver cirrhosis, using diagnostic imaging tools. World J Hepatol. 2015 Aug 187(17):2069-79. doi: 10.4254/wjh.v7.i17.2069.
Rastogi A; Liver transplant biopsy interpretation: Diagnostic considerations and conundrums. Indian J Pathol Microbiol. 2022 Apr-Jun65(2):245-257. doi: 10.4103/ijpm.ijpm_1090_21.