Decreased Activity of Plasma ADAMTS13 May Contribute to the Development of Liver Disturbance and Multiorgan Failure in Patients with Alcoholic Hepatitis

• Published in: Alcoholism, clinical and experimental research Vol. 29; no. s3; pp. 264S - 271S
• Main Authors: Uemura, Masahito, Matsuyama, Tomomi, Ishikawa, Masatoshi, Fujimoto, Masao, Kojima, Hideyuki, Sakurai, Shinya, Ishii, Sadanobu, Toyohara, Masahisa, Yamazaki, Masaharu, Yoshiji, Hitoshi, Yamao, Jyunichi, Matsumoto, Masanori, Ishizashi, Hiromichi, Fujimura, Yoshihiro, Fukui, Hiroshi
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2005; Lippincott Williams & Wilkins
• Subjects: ADAM Proteins - blood; ADAMTS13; ADAMTS13 Protein; Adult; Aged; Alcoholic Hepatitis; Alcoholism and acute alcohol poisoning; Algorithms; Bilirubin - blood; Biological and medical sciences; C-Reactive Protein - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis, Alcoholic - complications; Hepatitis, Alcoholic - metabolism; Hepatitis, Alcoholic - pathology; Humans; Liver - metabolism; Liver - pathology; Liver Cirrhosis, Alcoholic - complications; Liver Cirrhosis, Alcoholic - metabolism; Liver Cirrhosis, Alcoholic - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Microcirculatory Disturbance; Middle Aged; Models, Statistical; Multiorgan Failure; Multiple Organ Failure - etiology; Multiple Organ Failure - metabolism; Multiple Organ Failure - pathology; Other diseases. Semiology; Peptide Hydrolases - metabolism; Severe Alcoholic Hepatitis; Toxicology; Human; Digestive system; Enzyme; Alcoholism; Multiple organ failure; Microcirculatory Disturbance; Hepatic disease; Metalloendopeptidases; Biological activity; Blood plasma; Severe Alcoholic Hepatitis; Peptidases; Hepatitis; ADAMTS13; Multiorgan Failure; Development; Digestive diseases; Hydrolases; Alcoholic Hepatitis
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1097/01.alc.0000192326.08931.cb

: Background: The pathogenesis of alcoholic hepatitis (AH) remains unclear and the prognosis of severe alcoholic hepatitis (SAH) is very poor. Deficiency of von Willebrand factor (VWF)‐cleaving protease (VWF‐CP/ADAMTS13) results in an increase of the plasma unusually large VWF multimer and leads to platelet clumping, which causes microcirculatory disturbance and finally multiorgan failure. The aim of this study was to explore the potential role of ADAMTS13 on the development of liver disturbance and multiorgan failure in AH. Methods: The activity of plasma ADAMTS13 and its clinical correlation were determined in 14 patients with AH, 4 with SAH (Maddrey score, mean 62), and 10 with alcoholic liver cirrhosis (LC). Results: The activity of the plasma ADAMTS13 significantly decreased in patients with AH (mean 59%, p < 0.001), SAH (17%, p < 0.001) and LC (76%, p < 0.02) as compared with the healthy subjects (102%, n = 60). The activity was markedly lower in SAH than in AH (p < 0.02) and LC (p < 0.02). In three nonsurvivors with SAH who had multiorgan failure, it was extremely low (4.5%, 5.0%, and 16.0%, respectively), but in a survivor with SAH it remained mild decrease (44%). In AH, the protease activity increased at the recovery stage (42%→ 75%, p < 0.05). In the univariate analysis, the activity correlated with 10 clinical variables including functional liver capacity, inflammation signs, renal function, and platelet count in patients with AH and SAH. Among these, multivariate analysis showed that serum total bilirubin and C‐reactive protein independently correlated with the protease activity. Conclusion: The activity of plasma ADAMTS13 markedly decreased in SAH in addition to AH. The activity was closely related to hyperbilirubinemia and inflammation signs, and was extremely low in nonsurvivors with SAH and multiorgan failure. The marked decrease of plasma ADAMTS13 may, in part, contribute to not only the progression of liver disturbance in AH, but also the development of multiorgan failure in SAH through microcirculatory disturbance.