The emergence of hIPSCs (human Induced Pluripotent Stem Cells) and differentiation protocols to generate hepatocyte-like cells has opened the possibility of addressing these issues. Here we discuss the recent progress and potential in the production of various cell types constituting the liver and their applications to model liver diseases and test drug toxicity in vitro. This article is protected by copyright. All rights reserved. “
“The plight of liver disease is often complicated by bleeding and thrombotic diathesis. The forces of procoagulation and

anticoagulation, fibrinolysis and antifibrinolysis are in constant flux as a result of impaired liver function and insults that complicate PF-02341066 research buy liver disease. Our standard methods for assessing coagulation support the notion that liver disease is a bleeding disorder. The prothrombin time (PT) and activated partial Nutlin-3a clinical trial thromboplastin time (APTT) are prolonged, with the former being an important prognostic indicator in liver disease. However, these

and other conventional measures of individual protein levels are poor at estimating bleeding and thrombosis risk in this group of patients. Alternative testing, which takes into account the interplay between the various coagulant forces, can predict thrombosis and bleeding risk in patients with hepatic dysfunction. While

the basis for understanding coagulopathy has its roots in the traditional clotting cascade, this rigid pathway is now more complex than once thought. A number of coagulation proteins are synthesized by the liver and their synthesis is variably impaired in liver disease (see Table 1). Factor VII is the first protein to decrease when there is hepatocyte damage, likely due to its short half-life (approximately 2 h)1 and serum levels are inversely correlated with the degree of cirrhosis.2 Factors II, V and X are also reduced in acute liver injury, with additional deficiencies of factors IX and XI in chronic liver injury.3 Fibrinogen levels are within the normal range in stable selleck kinase inhibitor liver disease, but decreases occur as liver disease progresses, with concurrent dysfibrinogenemia.4 Conversely, plasma factor VIII levels are elevated in liver disease, despite decreased mRNA expression within the liver. This is likely secondary to enhanced vWF synthesis, which binds VIII and results in increased plasma vWF–VII complexes.5 These procoagulant protein deficiencies are counterbalanced by a deficit in anticoagulant proteins. These proteins are also synthesized within the liver, and their diminished circulating levels swing the coagulopathy pendulum in favor of clotting.