LIVER Frontline Gastroenterol: first published as 10.1136/flgastro-2018-101139 on 2 March 2019. Downloaded from REVIEW Medical liver biopsy: background, indications, procedure and histopathology Alexander Boyd, 1,2,3 Owen Cain,4 Abhishek Chauhan,1,2,3 Gwilym James Webb2,5 ► Additional material is ABSTRACT predominant pathology if more than one published online only. To view Histological analysis of liver tissue continues to cause of liver injury is present. Second, liver please visit the journal online (http:// dx. doi. org/ 10. 1136/ play an important role in modern hepatological biopsy allows assessment of disease severity flgastro- 2018- 101139). practice. This review explores the indications for including staging and grading.2 Staging 1 medical liver biopsy in addition to the procedure pertains to the severity of fibrosis: although Biomedical Research Centre, University Hospitals Birmingham itself, potential complications, preparation of non-invasive tests increasingly have a role NHS Foundation Trust and tissue and routine staining. A broad selection of to play, biopsy is generally considered the University of Birmingham, histological images is included to illustrate the ‘gold-standard’ test provided a satisfac- Birmingham, UK 2Centre for Liver and appearance of liver tissue both in health and in tory sample is obtained. Grading involves Gastrointestinal Research, several important diseases. determining the severity of the underlying Institute of Immunology and disease process. Immunotherapy, University of Birmingham, Birmingham, UK Biopsies are occasionally carried out in 3Liver Unit, University Hospitals INTRODUCTION acute liver failure. Biopsy in this setting Birmingham NHS Foundation Liver biopsy continues to play an impor- would be determined on a case-by-case Trust, Birmingham, UK 4 tant role in modern clinical practice. Biop- Histopathology, University basis; recent guidance suggests that it Hospitals Birmingham NHS sies can be ‘targeted’ (surgical) at a lesion can be considered to rule out infiltrative Foundation Trust, Birmingham, or ‘non-targeted’ (medical) to allow assess- malignancy, alcohol-related pathology UK 5 ment of the liver parenchyma in general. 3 Hepatology, Cambridge and cirrhosis. University Hospitals NHS This review discusses indications for Foundation Trust, Cambridge, UK medical liver biopsy, the procedure itself, PERFORMING A LIVER BIOPSY possible complications, sample prepara- Liver biopsies are usually obtained via a Correspondence to tion, staining and histological findings both http://fg.bmj.com/ Dr Alexander Boyd, NIHR percutaneous approach using ultrasound Birmingham Liver Biomedical in normal liver tissue and in several impor- guidance. Coagulopathy and thrombocy- Research Unit, Birmingham B15 tant diseases. A familiarity with histological topenia are common problems in patients 2GW, UK; alexander. boyd3@ appearances can improve understanding of nhs. net with liver disease and may pose an unac- pathophysiology and underpins good clin- ceptable risk for a percutaneous approach: Received 2 November 2018 ical decision-making. We have endeavoured in these cases, a trans-venous approach on September 27, 2021 by guest. Protected copyright. Revised 3 January 2019 to provide high-quality images to support Accepted 19 January 2019 can be used instead, avoiding puncture of the descriptions given. the liver capsule.4 For a trans-venous approach, the internal INDICATIONS FOR PERFORMING A jugular vein is normally used to introduce LIVER BIOPSY a catheter into one of the hepatic veins The advent of non-invasive tools such as under fluoroscopic guidance,5 and a biopsy serum biomarkers and elastography has needle is then advanced. This approach given clinicians additional tools for esti- reduces the risk of significant bleeding, 1 © Author(s) (or their mating the severity of fibrosis. While this although the core of tissue obtained may be 6 employer(s)) [year]. has resulted in reduced overall need for smaller and multiple needle passes needed. Re-use permitted under liver biopsy, histological analysis of the Other reasons for a trans-venous approach CC BY. Published by BMJ. hepatic parenchyma remains an important include ascites, simultaneous acquisition To cite: Boyd A, Cain O, investigation. of a hepatic venogram or pressure studies Chauhan A, et al. Frontline Broadly, the indications for medical liver and obesity or other anatomical consider- Gastroenterology Epub ahead of print: [please include Day biopsy fall into two groups. First, estab- ations where a safe percutaneous puncture Month Year]. doi:10.1136/ lishing a diagnosis, which includes ruling site cannot be identified. Biopsies can be flgastro-2018-101139 out other diagnoses or determining the obtained laparoscopically, although this is Boyd A, et al. Frontline Gastroenterology 2019;0:1–8. doi:10.1136/flgastro-2018-101139 1 LIVER Frontline Gastroenterol: first published as 10.1136/flgastro-2018-101139 on 2 March 2019. Downloaded from not routine in the UK and is often opportunistic due to Non–formalin-fixed tissue may be needed for tests the presence of a macroscopically abnormal liver. such as microbiological analysis or copper quantifi- In general, use of a 16G or wider cutting needle is cation studies.7 The standard initial stain is H&E,12 recommended for liver biopsy. The presence of 10–12 which stains nuclei blue and cytoplasm and fibrous portal tracts within the specimen is considered suffi- tissue pink. Other routine stains carried out are listed cient for reliable analysis,7 ensuring that architectural below in table 1.13 Immunohistochemistry is used in relationships between structures are maintained. The particular situations, some of which are mentioned in length of the biopsy specimen correlates with the the relevant sections later in the article. number of portal tracts,8 and therefore a length of 20–25 mm is preferred. Specimens which are subop- HISTOLOGICAL ASSESSMENT timal in size may result both in diagnostic inaccuracy 7 In a medical liver biopsy, the normal liver architec- and in the inaccurate assessment of disease severity. ture should be maintained unless there are marked morphological changes due to cirrhosis or necrosis. POTENTIAL COMPLICATIONS Usually areas of hepatic parenchyma with hepatocytes Liver biopsies are usually carried out as a day-case and sinusoids are seen (‘lobular’ region), which are admission, with bed rest and basic non-invasive moni- interspersed with central venules and portal tracts. toring following the procedure. Overnight admission Portal tracts usually contain a portal vein, a branch of may be warranted if the patient lives alone. Postproce- 13 9 the hepatic artery and a bile duct. dural pain is usually mild. The most significant risk is Three different ‘zones’ are defined by these struc- bleeding—this is often immediate but can present up 10 tures, although the anatomy is complex: zone 1 is adja- to 1 week after the procedure. Other risks include cent to the portal tract, zone 3 is closest to the hepatic haemobilia, non-hepatic organ puncture, infection and venule and zone 2 is in between (see figure 1). This reaction to local anaesthetic. arrangement of structures is also called an ‘acinus’.12 Severe bleeding following a percutaneous liver biopsy is usually intraperitoneal and haemodynamic insta- bility is common.7 A UK-wide audit in 2013 reported FIBROSIS a risk of clinically significant bleeding (with drop in Fibrosis is a dynamic process caused by chronic injury, blood count, radiological evidence of bleeding and inflammation and regeneration. This usually begins in requirement for intervention) of 0.4%. The mortality a particular area (eg, zone 1 in chronic biliary disease) rate was 0.11%,11 with bleeding the cause in all cases. and extends outwards as thin fibrous septa. These can then extend to adjacent portal tracts or central venules It is worth highlighting that targeted biopsy was linked 12 to a greater risk of major complications than non-tar- which is known as bridging fibrosis, a precursor to geted biopsy. cirrhosis. As the process advances further, the cirrhotic changes of distortion and nodule formation ensue. The STAINING use of stains (eg, HvG and orcein—see table 1) can help Liver biopsy specimens are fixed in formalin to to distinguish the presence of long-standing fibrosis, http://fg.bmj.com/ form cross-links and prevent degradation. Speci- which is associated with the formation of mature mens are then dehydrated and embedded in paraffin elastic fibres, from the collapse of normal architecture before microtome sectioning and mounting on slides. which can be seen in acute hepatitis with necrosis.13 on September 27, 2021 by guest. Protected copyright. Table 1 Summary of the routine stains used for a medical liver biopsy in addition to H&E Stain Material stained Relevance in liver biopsy Reticulin Type III collagen fibres Useful for assessing gross architecture of the specimen. Condensation of reticulin fibres is seen in areas of recent hepatocellular necrosis and in fibrosis Also useful for highlighting nodular changes in nodular regenerative hyperplasia Haematoxylin van Type I collagen fibres Normally only present in portal tracts and around hepatic veins; increased staining seen in fibrosis Gieson* Orcein Hepatitis B surface antigen May be present in chronic Hepatitis B infection Copper-associated protein Can be increased in any cause of chronic cholestasis and Wilson’s disease Elastic fibres Produced in longstanding fibrosis and can help differentiate this from