Stefanie Friedrich

Liver stiffness is directly influenced by central venous pressure

BACKGROUND & AIMS Liver stiffness (LS) as measured by transient elastography [Fibroscan] offers a novel non-invasive approach to assess liver cirrhosis. Since Fibroscan seems to be unreliable in patients with congestive heart failure, it remains to be determined whether hemodynamic changes affect LS irrespective of fibrosis. METHODS & RESULTS Using landrace pigs, we studied the direct relationship between the central venous pressure and LS measured by Fibroscan. Clamping of the inferior caval vein increased LS from 3.1 to 27.8kPa while reopening reversed LS within 5min to almost normal values of 5.1kPa. We then studied LS as a function of venous pressure in the isolated pig liver by clamping the upper and lower caval, portal vein and hepatic artery. The stepwise increase of intravenous pressure to 36cm of water column (3.5kPa) linearly and reversibly increased LS to the upper detection limit of 75kPa. We finally measured LS in 10 patients with decompensated congestive heart failure before and after recompensation. Initial LS was elevated in all patients, in 8 of them to a degree that suggested liver cirrhosis (median 40.7kPa). Upon recompensation with a median weight loss of 3.0kg, LS decreased in all 10 patients down to a median LS of 17.8kPa. Inflammation could not account for increased LS since initial liver enzyme counts were only slightly elevated and did not change significantly. CONCLUSION LS is a direct function of central venous pressure which should be considered when assessing the degree of fibrosis.

413 INCREASED LIVER STIFFNESS IN ALCOHOLIC LIVER DISEASE: DISSECTING FIBROSIS FROM STEATOHEPATITIS

413 INCREASED LIVER STIFFNESS IN ALCOHOLIC LIVER DISEASE: DISSECTING FIBROSIS FROM STEATOHEPATITIS S. Mueller, G. Millonig, S. Friedrich, F. Stickel, T. Longerich, P. Schirmacher, H.-K. Seitz. Center for Alcohol Research and Salem Medical Center, University of Heidelberg, Heidelberg, Germany; Clinical Pharmacology, University of Bern, Bern, Switzerland; Institute of Pathology, University of Heidelberg, Heidelberg, Germany E-mail: sebastian.mueller@urz.uni-heidelberg.de

17 Extrahepatic Cholestasis Increases Liver Stiffness (Fibroscan ®) Irrespective of Fibrosis

Transient elastography (FibroScan [FS]) is a novel non-invasive tool to assess liver fibrosis/ cirrhosis. However, it remains to be determined if other liver diseases such as extrahepatic cholestasis interfere with fibrosis assessment because liver stiffness is indirectly measured by the propagation velocity of an ultrasound wave within the liver. In this study, we measured liver stiffness immediately before endoscopic retrograde cholangiopancreatography and 3 to 12 days after successful biliary drainage in patients with extrahepatic cholestasis mostly due to neoplastic invasion of the biliary tree. Initially elevated liver stiffness decreased in 13 of 15 patients after intervention, in 10 of them markedly. In three patients, liver stiffness was elevated to a degree that suggested advanced liver cirrhosis (mean, 15.2 kPa). Successful drainage led to a drop of bilirubin by 2.8 to 9.8 mg/dL whereas liver stiffness almost normalized (mean, 7.1 kPa). In all patients with successful biliary drainage, the decrease of liver stiffness highly correlated with decreasing bilirubin (Spearman’s 0.67, P < 0.05) with a mean decrease of liver stiffness of 1.2 0.56 kPa per 1 g/dL bilirubin. Two patients, in whom liver stiffness did not decrease despite successful biliary drainage, had advanced liver cirrhosis and multiple liver metastases, respectively. The relationship between extrahepatic cholestasis and liver stiffness was reproduced in an animal model of bile duct ligation in landrace pigs where liver stiffness increased from 4.6 kPa to 8.8 kPa during 120 minutes of bile duct ligation and decreased to 6.1 kPa within 30 minutes after decompression. Conclusion: Extrahepatic cholestasis increases liver stiffness irrespective of fibrosis. Once extrahepatic cholestasis is excluded (e.g., by liver imaging and laboratory parameters) transient elastography is a valuable tool to assess liver fibrosis in chronic liver diseases. (HEPATOLOGY 2008;48:1718-1723.)