[65, 67-70] Splenectomy resulted in both the increment of platelets and the improvement of liver functions, including serum total bilirubin levels, albumin levels, and prothrombin times in cirrhotic patients with thrombocytopenia and hypersplenism.[68-70] In reports with regard to long-term

effects, the improvement of liver function was maintained for more than 6 months after surgery in patients with CLD and cirrhosis.[65, 67] Platelet transfusion is an established therapy for thrombocytopenia with well-known benefits and complications.[71] Maruyama et al. recently reported that platelet transfusion improved some of the indicators of liver function including serum albumin, cholinesterase, and hyaluronic acid in patients with CLD and cirrhosis, who had thrombocytopenia.[32] SP600125 in vivo The result suggests that not only endogenous platelets but exogenous platelets could play a role in the improvement of liver function, although whether platelet transfusion is appropriate for check details CLD patients with thrombocytopenia is still unclear even in the published guideline for platelet transfusion.[64] Platelet increment therapies, such as administration of TPO receptor agonist, splenectomy, and platelet transfusion are reported to have adverse effects while they have ameliorating effects on CLD and cirrhosis.[62, 72-75] Portal vein thrombosis was observed among patients who received

eltrombopag or splenectomy.[62, 72] In addition, operative complications of splenectomy include hemorrhage, infection, and injury to the pancreatic tail.[73] In platelet transfusion, platelets are frequently activated and may induce inflammatory reactions and unexpected side-effects including febrile non-hemolytic reactions and acute lung injury.[74, 75] There are some reports about the detrimental effects of platelets on CLD and cirrhosis. Zaldivar et al. provided evidence that chemokine (C-X-C motif) ligand 4 (CXCL4), known as a platelet-derived factor, modulated liver fibrosis in animal models of chronic liver injury in vivo, although a direct release of CXCL4 by platelets was not demonstrated.[35] In addition, the proliferation and chemotactic migration of HSCs was MCE公司 significantly enhanced by CXCL4 without the

synthesis of collagen and the expression of TGF-β in vitro.[35] As one of the side-effects of platelet increment therapy, promotion of liver carcinogenesis should be considered because of the high risk of HCC in patients with CLD and cirrhosis.[3] Carr et al. reported that patients with thrombocytosis (platelet levels > 400 × 109/L) had larger size of HCC and better liver function than patients with platelets in the normal range.[76] Sitia et al. demonstrated that the antiplatelet drugs reduced the development of HCC in a mouse model of chronic hepatitis B virus infection, although this approach was not effective in the carbon tetrachloride-induced cirrhosis model.[77] These findings indicate that platelets might have a promotive effect on liver carcinogenesis.