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Patients with primary sclerosing cholangitis (PSC) tend to develop progressive liver fibrosis and end-stage liver disease within 10-20 years. The International PSC Study Group declared research on surrogate endpoints a high-priority task not least for ongoing clinical trials on novel treatment options. The spleen in patients with PSC often enlarges even before cirrhosis develops. Transient elastography (TE) has been investigated as a dynamic and prognostic marker in PSC. However, TE is not generally accessible, measures only a small part of the right liver, and is prone to errors in obese patients, and liver stiffness is related to postprandial status, liver inflammation, and biliary obstruction. We have recently demonstrated that single-point spleen length (SL) measurement has a prognostic performance similar to liver stiffness measured by TE. SL measurement is a fast, simple, and ubiquitously available method. However, absolute spleen size depends on body height and sex, and single-point measurement of SL cannot be used to assess the effects of therapeutic interventions. To overcome these issues, we assessed the intra-individual development of spleen size over time (delta spleen length: dSL = SL - SL) to evaluate its role as a novel surrogate marker, which accounts for the dynamic nature of PSC progression.