The Royal College of Pathologists 'Tissue Pathway for the Investigation of Medical Liver Disease' is currently being revised, providing the authors with the opportunity to review updated literature, identify changes in practice (since the current edition was released), and consider how we could improve our practice.

The liver biopsy remains a critical tool in the diagnosis and assessment of medical liver disease; however, variation in reporting practices can reduce its clinical impact and interpretability. Unlike oncological pathology, the complexity and breadth of medical liver disease do not readily lend themselves to a rigid “minimum dataset” approach. Nevertheless, a reporting template offers a practical framework that can help promote a degree of consistency, while preserving the flexibility required for a nuanced clinicopathological interpretation. Such an approach can support both specialist and non-specialist pathologists ensure a comprehensive report, but also help our medical and hepatology colleagues easily identify diagnostic and prognostic details pertinent to the patient treatment pathway.

A core panel of histochemical stains are used routinely across all centres to supplement the H&E interpretation, although there is variation in stain selection between institutions. This session will review the diagnostic utility of commonly employed special stains, highlighting their diagnostic utility and highlight common interpretive pitfalls encountered in everyday practice.

The RCPath tissue pathways document for liver biopsy reporting attempts to standardise nomenclature, acknowledging that pathologists and hepatologists might use the same word to mean different things, and usefully defines patterns of injury in acute and chronic scenarios.
The 4 patterns of acute injury are; 1, lobular hepatitis – a distinctive pattern of injury but not specific for aetiology, 2, canalicular bile plugging/bilirubinostasis/bland cholestasis – again a distinctive pattern of injury, an indicator of drug induced liver injury as the first consideration , not to be confused with the chronic biliary disease pattern (a patient with cholestatic LFTs often has no visible bile stasis in their biopsy), 3, simple steatosis – a presumed reversible injury to be separated from potentially progressive steatohepatitis, and 4, acute outflow obstruction – rare but important to recognise.
These patterns provide a useful starting point but not all liver injury will fit neatly into the described categories.
Recognising an acute pattern of injury is not always easy, necrosis versus fibrosis for example, there is a need for good connective tissue stains, mature fibrosis will contain elastin. Necrosis is not always accompanied by hepatitis in viable parenchyma. Acute patterns of injury can sometimes be seen on a background of chronic disease/fibrosis. Example cases to illustrate these points will be discussed.

Chronic hepatitis and chronic biliary disease are characterised by predominantly portal tract-based histopathological changes within liver biopsies. Both groups of conditions typically show chronic inflammation within portal tracts, with varying degrees of interface hepatitis. Both can lead to portal tract fibrosis, bridging fibrosis and cirrhosis. The most commonly encountered form of chronic hepatitis in the UK is autoimmune hepatitis (AIH). The inflammatory cel infiltrate in AIH is typically plasma cell-rich. Disease activity in AIH is assessed e.g., via the severity of interface hepatitis and of parenchymal necroinflammation (the latter may be severe in “acute” or “acute-on-chronic” AIH). The differential diagnoses of a chronic hepatitis picture include chronic viral hepatitis (especially hepatitis B and C, which are less commonly encountered nowadays in UK liver pathology practice) and a drug-induced liver injury (DILI). A DILI due e.g., to nitrofurantoin or etretinates, can closely mimic idiopathic AIH. The two most commonly encountered forms of chronic biliary disease are primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Signs of chronic biliary disease in liver biopsies include portal tract expansion, with periductal (“onion skin”) fibrosis classically seen in PSC; and more dense portal tract chronic inflammation, often with granulomas, seen in PBC. Identification of copper (e.g., using a rhodanine stain) or copper-associated protein (e.g., using orcein or Victoria blue stains) within periportal hepatocytes can help to support a diagnosis of chronic biliary tract disease, while highlighting of native bile ducts, a ductular reaction and intermediate hepatobiliary cells using cytokeratin 7 immunohistochemistry can also provide valuable evidence for these conditions. Cholestasis is usually seen only in end-stage disease or in PSC involving large bile ducts. Overlap conditions with features of both AIH and either PSC or PBC can be defined using clinical and histopathological criteria and identification of these may have important clinical implications.