A liver biopsy is not anymore regarded as mandatory for the diagnosis of PBC in patients with elevated serum markers of cholestasis and positive serum AMA [28, 29] , but may be helpful in excluding other potential causes of cholestatic disease and in assessing disease activity and stage. A liver biopsy may also be helpful in the presence of disproportionally elevated serum transaminases and/or serum IgG levels to identify additional or alternative processes. Histological staging of PBC (stage 1 to stage 4) is determined by the degree of (peri)portal inflammation, bile duct damage and proliferation, and the presence of fibrosis/cirrhosis according to Ludwig et al. [52] and Scheuer [53] . Stage 1 disease is characterized by portal inflammation with granulomatous destruction of the bile ducts, although granulomas are often not seen. Stage 2 is characterized by periportal hepatitis and bile duct proliferation. Presence of fibrous septa or bridging necrosis is defined as stage 3 and cirrhosis as stage 4 [52] . Findings of fibrotic or cirrhotic changes (stage 3 or 4) are accompanied by a worse prognosis [54] . Florid duct lesions as defined by focal duct obliteration and granuloma formation are regarded as typical for PBC. The liver is not uniformly involved, and features of all four stages of PBC can be found in one biopsy specimen. The most advanced histological features are used for histological staging.