Thrombopoietin levels in serum and liver tissue in patients with chronic viral hepatitis and hepatocellular carcinoma

Abstract

Thrombocytopenia in liver diseases is considered to be due to splenic platelet pooling and accelerated destruction. Since thrombopoietin (TPO), a regulator of thrombopoiesis, is produced mainly in the liver, decreased production of TPO may account for thrombocytopenia in liver diseases. To address this issue, we measured serum TPO, using a sensitive sandwich ELISA, in 108 patients with chronic viral hepatitis, which included chronic hepatitis (CH) and liver cirrhosis (LC), and hepatocellular carcinoma (HCC), and in 29 normal controls. TPO mRNA in 78 liver samples was examined by reverse transcription (RT)-PCR. Platelet counts in CH, LC, HCC and controls were 176 +/- 15 x 10(9)/l, 81 +/- 8 x 10(9)/l, 99 +/- 7 x 10(9)/l and 234 +/- 9 x 10(9)/l respectively. Serum TPO levels in CH, LC and HCC were 2.79 +/- 0.4 fmol/ml, 1.49 +/- 0.2 fmol/ml and 1.97 +/- 0.2 fmol/ml, and were higher than those of controls. Serum TPO levels were positively correlated with prothrombin time and serum albumin (P < 0.05, in each case), and negatively correlated with Indocyanine Green test and Pugh score (P < 0.01 and P < 0.05 respectively). However, RT-PCR and immunohistochemistry showed that expression of TPO mRNA and protein were similar in the different liver diseases, suggesting that serum TPO is a reflection of the total mass of functional liver. Platelet counts were negatively correlated with spleen index, but not with serum TPO. These results suggest that thrombocytopenia in liver disease is not directly associated with serum TPO but is associated with hypersplenism.

Transient thrombopoietin peak after liver transplantation for end‐stage liver disease

“…Further evidence that, in virally infected patients, the thrombocytopenia was, at least in part, extracorpuscularily immune-mediated, comes from our observation of splenomegaly and platelet count in groups B and C (hepatitis B and C infections) (not statistically significant), whereas, in contrast, the significance between splenomegaly and thrombocytopenia in nonviral diseases (PBC and alcohol-induced) suggests a direct platelet-retaining effect of the enlarged spleens. In contrast to a recent Japanese study (Okubo et al, 2000) that found a significant correlation between platelet count and splenomegaly, we only can confirm this relationship in non-viral liver disease (groups A and D); the serum TPO levels in the Japanese study were also reduced in less severe liver disease stages. These findings might be relevant in substitutive treatment of thrombocytopenic liver diseased patients with TPO.…”

“…However, clinical standard committees are reluctant to favour either serum or plasma for quantitation of TPO. Experiments that spike either material with TPO, in the quest for the ideal sample type for enzymelinked immunosorbent assay (ELISA), are still rare, with serum being used more frequently nowadays for quantitative TPO estimation, (Shimodaira et al, 1996;Okubo et al, 2000;Peck-Radosavljevic et al, 2000). However, the consistent peak values in the four patient groups as well as the low interassay variability suggest that serum is as good an analyte as plasma.…”

Hematologic Safety of Breast Cancer Chemotherapies in Patients with Hepatitis B or C Virus Infection

“…A decrease in hepatic TPO production has been proposed as an important concomitant cause of the reduction in platelet production in patients with chronic liver disease. Some studies have shown that TPO production correlates with disease stage and liver function in patients with chronic liver disease [21,22]. In this study, it can be presumed that most patients did not experience a decrease in TPO, because almost all patients with HBV and/or HCV infection had normal baseline liver function.…”

Correlation Between Serum Thrombopoietin Level and Cirrhosis Clinical Stage in Liver Cirrhosis Patients in Mohammad Hoesin Palembang Hospital and Palembang BARI Hospital

“…This result was similar to Stockelberg et al, Goulis et al with correlation that reported no correlation between serum TPO level and platelet counts in liver cirrhosis. 9,14,16 This result correlation between serum TPO level and platelet counts in liver cirrhosis patients, showed by a low serum TPO level in thrombocytopenia patients rather than normal platelet patients. In contrast, Tamel et al reported that serum TPO was correlate negatively with platelet counts in liver cirrhosis patients (r = -0.71; p < 0.001).…”

“…Serum TPO level also correlate to clinical lower serum TPO the more severe its liver cirrhosis. [8][9][10][11][12] Otherwise, several studies (Temel et al, Stockelberg et al, and Yilmaz et al) showed that serum TPO in liver cirrhosis and liver fibrosis patients was not found to be lower than healthy individual and did [8][9][10][11][12][13][14][15][16] Serum TPO were mainly regulated by total mass of platelet and circulating megakaryocyte by receptor mediated clearance mechanism. [17][18][19] TPO was a main regulator of platelet production, so that serum TPO become a recommended laboratory test to evaluate liver cirrhosis patients with thrombocytopenia.…”