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Thrombopoietin (TPO) deficiency has been proposed as an important etiologic factor for thrombocytopenia in advanced-stage liver disease. To clarify the contributions of platelet production, platelet consumption, coagulation activation, and splenic sequestration to thrombocytopenia in liver disease, we studied TPO serum levels and markers of platelet production, platelet activation, and coagulation activation before and 14 days after orthotopic liver transplantation (OLT) in 18 patients with advanced liver cirrhosis. Thrombocytopenia before transplantation occurred with low-normal serum levels of TPO, normal levels of platelet and coagulation activation markers, and no increase in bone marrow production of platelets. TPO serum levels increased significantly on the first day after OLT, preceding the increase of reticulated platelets by 3 days and peripheral platelets by 5 days. Normalization of the peripheral platelet count occurred in most patients within 14 days of OLT, irrespective of the change in spleen size assessed by computed tomography volumetry. Normalization of platelet counts was not hampered by a certain degree of platelet activation observed during the steepest increase in the peripheral platelet count. Bone marrow production of platelets increased significantly within 2 weeks of transplantation. Low TPO serum levels with low platelet counts and without platelet consumption suggests low TPO production in end-stage liver disease. The rapid increase in TPO serum levels after transplantation induces an increase in the bone marrow production of platelets. Decreased TPO production in the cirrhotic liver is an important etiologic factor for thrombocytopenia in liver disease that is rapidly reversed by transplantation.

Thrombocytopenia is common in advanced-stage liver disease and is partly caused by inadequate thrombopoietin (TPO) production in the failing liver. Treatment of chronic hepatitis C with interferon alfa (IFN-␣) often induces thrombocytopenia, sometimes even leading to discontinuation of treatment. TPO regulation in response to IFN-␣-induced thrombocytopenia was studied in patients with chronic hepatitis C with and without cirrhosis (Child A). An in vitro culture system with HepG2 cells was used to demonstrate any direct effects of IFN-␣ on TPO mRNA expression, TPO synthesis, or TPO secretion from liver cells. Thrombocyte count was lower (U test: P F .05) in patients with hepatitis C cirrhosis compared with patients with chronic hepatitis C without cirrhosis before IFN therapy, and decreased in both patient groups (Wilcoxon matched-pairs test: P F .05) on IFN therapy, the median decrease in both groups being comparable (noncirrhotic patients, 35%; cirrhotic patients, 32%; U test: P ‫؍‬ .57). TPO levels rose in noncirrhotic patients (Wilcoxon matchedpairs test: P F .05), but not in patients with cirrhosis (noncirrhotic patients' median increase: 43% vs. cirrhotic patients' median decrease: 5%; U test: P F .001). Even in patients without cirrhosis, the increase in TPO levels was relatively small for the decrease in platelet count. No effect of IFN-␣ could be demonstrated on TPO mRNA expression in vitro, but TPO secretion from liver cells was significantly reduced. Lower platelet counts but similar TPO levels in patients with chronic hepatitis C and cirrhosis compared with noncirrhotic patients and a moderate increase in TPO levels in noncirrhotic patients with a missing increase in cirrhotic patients during IFN-␣-induced thrombocytopenia provide further evidence for an impairment of TPO production in patients with cirrhosis and during IFN therapy.Recombinant human TPO could be of value in patients developing severe thrombocytopenia under IFN-␣ therapy. (HEPATOLOGY 1998;28:1424-1429.)Interferon alfa (IFN-␣) therapy is the current treatment of choice for chronic hepatitis C. Although well tolerated in many cases, IFN therapy has its side-effects, one of them being the development of thrombocytopenia. 1-3 Thrombocytopenia is mild in most cases, amounting to a decrease in peripheral platelet count between 10% and 50%, but when severe, can lead to bleeding complications 4,5 and discontinuation of IFN treatment. 6 Bone marrow suppression by IFN seems to be the main mechanism leading to thrombocytopenia in these patients, 7-9 and discontinuation of IFN therapy usually leads to restitution of a normal peripheral platelet count within 2 weeks.We recently described that inadequate thrombopoietin (TPO) production is at least partly responsible for thrombocytopenia in cirrhosis. 10 Because TPO is the key hematopoietic growth factor for full megakaryocyte maturation and thrombocyte production, 11 and the liver is the main source for TPO in humans, 12 a reduced production of TPO in the failing liver would lead to a lower peripher...

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Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.