Increased von Willebrand Factor Over Decreased ADAMTS13 Activity May Contribute to the Development of Liver Disturbance and Multiorgan Failure in Patients With Alcoholic Hepatitis

Abstract

The enhanced production of UL-VWFM over deficient activity of ADAMTS13 may, in part, contribute to not only the progression of liver injury but also the development of multiorgan failure through microcirculatory disturbance in SAH in addition to AH. The imbalance between the plasma ADAMTS13 activity and VWF:Ag could be a useful prognostic marker in AH.

Crucial Role of ADAMTS13 Related to Endotoxemia and Subsequent Cytokinemia in the Progression of Alcoholic Hepatitis

“…ADAMTS13:AC was markedly decreased in fatal SAH cases with multiorgan failure, in contrast to a mild-to-moderate decrease in SAH and AH survivors (Fig. 2a) (Uemura et al, 2005b;Matsuyama et al, 2007). Interestingly, ADAMTS13:AC in fatal SAH cases with multiorgan failure was extremely low, which is consistent with typical TTP.…”

“…During recovery, ADAMTS13:AC returned to a normal range, and both VWF:AG levels and levels of VWF:AG relative to ADAMTS13:AC decreased in AH and SAH survivors; however, in fatal SAH cases, the activity remained extremely low while the VWF:AG levels were still high, resulting in an extremely high ratio of VWF:AG to ADAMTS13:AC (Matsuyama et al, 2007;Uemura et al, 2005b). These results suggest that plasma ADAMTS13:AC and its substrate, VWF:AG, are closely correlated with the severity of liver disturbance and may be useful markers for predicting the clinical outcome of AH, especially in SAH with multiorgan failure.…”

“…* p<0.05, ** p<0.01, and *** p<0.005 significantly different between the two groups. (Partially modified from Uemura et al, 2005b andMatsuyama et al, 2007).…”

“…In this review, we will address interesting findings from our previous studies showing that plasma ADAMTS13:AC and its related parameters are potentially involved in the severity of liver disturbances and the development of multiorgan failure in patients with AH (Ishikawa et al, 2010;Matsuyama et al, 2007;Uemura et al, 2005b;Uemura et al, 2008b). We will focus on the importance of ADAMTS13 determination for a better understanding of pathophysiology and/or for possible therapeutic approaches of ADAMTS13 supplementation in this disease.…”

“…Since HSCs were shown to be the major producing cells of ADAMTS13 in the liver (Uemura et al, 2005a), much attention has been paid to the potential role of ADAMTS13 in the pathophysiology of liver diseases associated with sinusoidal and/or systemic microcirculatory disturbances (Feys et al, 2007;Ishikawa et al, 2010;Ko et al, 2006;Kobayashi et al, 2009;Lisman et al, 2006;Matsuyama et al, 2007;Okano et al, 2010;Park et al, 2002;Pereboom et al, 2009;Uemura et al, 2005b;Uemura et al, 2008a;Uemura et al, 2008b;Uemura et al, 2010;Yagita et al, 2005). ADAMTS13:AC is significantly decreased in patients with hepatic veno-occlusive disease (VOD) Park et al, 2002), AH (Ishikawa et al,2010;Matsuyama et al, 2007;Uemura et al, 2005b, Uemura et al, 2008b, LC (Feys et al, 2007;Uemura et al, 2008a), and patients undergoing living-donor related liver transplantation (Ko et al, 2006;Kobayashi et al,2009;Pereboom et al, 2009) and partial hepatectomy (Okano et al,2010). Furthermore, hepatitis C virus (HCV)-related LC patient with ADAMTS13 inhibitor (ADAMTS13:INH) typically develops TTP (Yagita et al, 2005).…”