Interferon increases serum thrombopoietin in patients with chronic hepatitis C

Shiota, Goshi; Okubo, Michiko; Kawasaki, Hironaka; Tahara, Tomoyuki

doi:10.1046/j.1365-2141.1997.552705.x

Cited by 24 publications

(14 citation statements)

References 9 publications

(18 reference statements)

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“…These results confirm the hypothesis of Kuter et al [15] that TPO mediates the feedback loop between circulating platelets and bone marrow megakaryocytes, and that serum levels of TPO are directly determined by the ability of platelets to remove TPO from the circulation. Indeed, serum TPO was inversely correlated with platelet count in patients following chemotherapy [28] and in patients treated with interferon [29]. Thus TPO may increase in response to a reduction in platelet numbers in humans.…”

Section: Discussionmentioning

confidence: 98%

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

Okubo

SHIOTA²,

KAWASAKI

2000

Clinical Science

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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.

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Section: Discussionmentioning

confidence: 98%

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

Okubo

SHIOTA²,

KAWASAKI

2000

Clinical Science

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“…There have been no reports regarding the relationship between platelet counts and the change of spleen size after IFN therapy. Bizollon et al [22] reported that biochemical and virological responder to combination therapy of ribavirin and IFN associated with marked histological improvement and Shiota et al [23] reported that serum TPO levels increased following SVR to IFN therapy in patients with chronic hepatitis C. Itoh et al [24] showed a significant decrease in fibrosis stage paralleled by an increase in platelet count and serum TPO levels in patients with SVR to IFN therapy after 4 years of follow-up. We also recently reported that the increase of platelet counts and serum albumin and decrease of ZTT associated with improvement of fibrosis in CH-C patients with SVR to IFN therapy [18].…”

Section: Discussionmentioning

confidence: 96%

Factors regarding increase of platelet counts in chronic hepatitis C patients with sustained virological response to interferon—Relation to serum thrombopoietin levels

Yagura

Tanaka

Tokita

et al. 2005

Hepatology Research

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“…TPO concentrations were found [12,13,16,31,35] (Table 2). Thrombocytopenic patients with severe hepatic diseases, however, showed less pronounced or no increase in the TPO level which might be due to an impaired TPO synthesis in the hepatocytes [15,16,21,38].…”

Section: Controlsmentioning

confidence: 98%

“…In patients with chronic hepatitis C but without liver cirrhosis Shiota et al [31] observed during an interferon therapy elevated serum TPO concentrations as compared to normal individuals while the blood platelet counts were in normal range. Intramuscular or intravenous IFN administration caused during the first week of the therapy a significant decrease in platelet count and a significant increase in the TPO concentration of the serum, the relationship between both parameters were comparable to those of patients without liver disease.…”

Section: Controlsmentioning

confidence: 98%

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Alteration of serum thrombopoietin levels in patients with chronic hepatitis C under interferon therapy

Wenzel

Gruber²,

Giers³

2010

Clinical Hemorheology and Microcirculation

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Thrombocytopenia is commonly observed during interferon-α (IFN-α) therapy in patients with chronic hepatitis C. Since thrombopoietin (TPO) is the main regulator of thrombopoiesis, thrombocytopenia may partially be due to a reduced TPO generation. Because of the developments of the second generation of TPO mimetic drugs patients with reduced TPO levels should be identified possibly having a benefit by medicinal stimulation of thrombopoiesis. Therefore, platelet count and serum TPO concentration of patients receiving an interferon-α therapy were determined.Twelve patients treated with IFN-α (daily 10 × 10 6 IU s.c. for four weeks) in cause of chronic hepatitis C were examined during the first month of therapy. Serum TPO concentration significantly decreased from 80.8 ± 48.0 to 34.6 ± 24.5 pg/ml (p < 0.05, Mann-Whitney test), and platelet count declined from 214,417 ± 48,292 to 151,333 ± 44,726 platelets/µl. During the following three weeks platelet count remained at a low level, while serum TPO increased to normal range.In conclusion, an interferon treatment causes reduced serum TPO level during the first week of therapy accompanied by decreased platelet count. The reduction in TPO synthesis contributes to the development of thrombocytopenia in patients during interferon therapy.

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Interferon increases serum thrombopoietin in patients with chronic hepatitis C

Cited by 24 publications

References 9 publications

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

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

Factors regarding increase of platelet counts in chronic hepatitis C patients with sustained virological response to interferon—Relation to serum thrombopoietin levels

Alteration of serum thrombopoietin levels in patients with chronic hepatitis C under interferon therapy

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