The recent change in steatotic liver disease (SLD) nomenclature does not affect routine diagnostic pathology practice and histopathology reporting. Liver biopsy is still the reference standard for assessing severity of activity and fibrosis in SLD, independent of subtype (metabolic dysfunction associated-MASLD/metabolic and alcohol-related-MetALD/alcohol related liver disease-ALD). Consensus position statements and an atlas for the standardized application of grading and staging systems in MASLD have been published. EPoS staging, an expanded 7-tiered (0-6) staging system for MASLD, is reproducible and accurately reflects liver tissue collagen quantitation and non-invasive liver fibrosis tests. The SALVE grading and staging system for ALD is validated, reproducible and prognostically relevant. Fully automated software applications are used in MASLD research and clinical trials alongside traditional histopathology scoring.

Vascular liver diseases are a rare, heterogeneous group of diseases that are often diagnosed late. Portal vein-based disease is often due to portal vein thrombosis but may also precede or occur in the absence of thrombosis. Hepatic vein-based disease occurs in association with chronic right heart failure and Budd-Chiari syndrome but shares features with sinusoidal obstruction. The Congestive Hepatic Fibrosis Score has been developed to assess fibrosis in congestive hepatopathy secondary to chronic right heart failure. Porto-sinusoidal vascular disorder (PSVD)/non-cirrhotic portal fibrosis (NCPF) is a new clinical entity broadening the spectrum of non-cirrhotic portal hypertension and is often under-recognised. Currently, there is a growing interest in identifying patients at increased risk and a liver biopsy >15 mm long is fundamental for PSVD/NCPF diagnosis. In a recent multi-society consensus, major histological criteria for the diagnosis of PSVD/NCPF in non-cirrhotic liver are nodular regenerative hyperplasia (NRH), muscularized portal venules and portal venule stenosis in ≥50% of portal tracts, while minor criteria are regenerative changes without NRH, abnormal distribution of vascular structures and portal venule stenosis in <50% of portal tracts.

Drug-induced liver injury (DILI) typically manifests as an acute hepatitis or acute cholestasis pattern on liver biopsy. Some drugs may also show features of steatohepatitis or vascular injury (e.g., nodular regenerative hyperplasia). Although DILI is not a common cause of chronic hepatitis or chronic cholangiopathy, increasing evidence indicates that some drugs can present with autoimmune hepatitis (AIH)–like hepatitis or chronic cholangiopathy mimicking primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).

Drug-induced autoimmune-like hepatitis (formerly termed drug-induced AIH) shares many features with classical AIH. Autoantibodies, interface hepatitis, and plasma cell aggregates are commonly observed. The most reliable discriminator between drug-induced autoimmune-like hepatitis and classical AIH is the presence or absence of relapse after withdrawal of immunosuppressive therapy. Histologically, advanced fibrosis (e.g., Ishak stage ≥4) favours classical AIH. Only 10–20 drugs are known to cause AIH-like hepatitis; commonly implicated agents in current practice include nitrofurantoin, minocycline, tetracycline, statins and infliximab.

Long-term recreational use of ketamine causes diffuse biliary injury, and ketamine-associated cholangiopathy is a great mimicker of PSC. It is characterised by diffuse narrowing of the intrahepatic bile ducts, with histological features of chronic cholangiopathy, periductal fibrosis or bile duct loss.

Checkpoint inhibitor–induced liver injury is now well recognised. Whereas liver biopsy was previously performed mainly for diagnostic purposes, current indications include treatment resistance (lack of response to immunosuppression) and suspected biliary involvement. Histologically, checkpoint inhibitor–induced liver injury typically shows panlobular hepatitis or confluent necrosis with prominent CD8-positive T lymphocytes. Cases with checkpoint inhibitor–induced cholangitis may demonstrate PBC-like cholangitis, PSC-like periductal fibrosis, or florid ductular reactions secondary to large-duct obstruction. As approximately 20% of cases show no abnormalities on MRCP, liver biopsy is useful when biliary involvement is suspected.