Study of serum thrombopoietin in patients with chronic hepatitis C virus infection

ABSTRACT

The aim of this study is to measure serum thrombopoietin [TPO] levels in patients with chronic active hepatitis C and post-hepatitis C liver cirrhosis, and examine the relationship between serum thrombopoietin concentration and the clinical stage of the disease, spleen index, circulating platelet counts, and liver functions in liver cirrhosis. One hundred and seventeen patients with chronic liver disease related to hepatitis C virus [44 with chronic active hepatitis C and 73 with liver cirrhosis] were selected, as a study group, from those admitted at the Internal Medicine Department of Benha University Hospitals. Their ages ranged from 37 to 62 years. Diagnosis of chronic active hepatitis C virus was based on the presence of positive HCV antibodies by 3[rd] generation ELISA [enzyme linked immunosorbant assay], abnormal elevation of serum transaminases for longer than 6 months, confirmed by positive HCV RNA by polymerase chain reaction [PCR] and liver biopsy which shows the stigmata of chronic hepatitis. Thirty healthy subjects were selected as a control group and matched with the study group regarding age, sex and residence. The mean levels of serum thrombopoietin in patients with chronic active hepatitis [CAH] were significantly higher than the control group [117.5 +/- 14.59 pg/ml, vs 99.8 +/- 11.03 pg/ml; P<0.001 respectively] while the mean levels of serum thrombopoietin were lower in cirrhotics than in CAH and the controls [82.82 +/- 20.7 pg/ml vs 117.5 +/- 14.59 pg/ml and 99.8 +/- 11.03 pg/ml; P<0.001 respectively]. In patients with liver cirrhosis, the mean levels of thrombopoietin decreased as the disease progressed [94.4 +/- 4.8 pg/ml in patients at Child-Pugh stage A, 73.4 +/- 10.5 pg/ml in patients at stage B and 45.1 +/- 5.6 pg/ml in patients at stage C] with statistical significant difference in-between them [P<0.001]. Thrombocytopenia [TCP] was found in 47 out of 73 [64.4%] of patients with liver cirrhosis. The mean levels of TPO in cirrhotics with TCP were significantly lower than cirrhotics without TCP [74.1 +/- 20.9 pg/ml vs 98.6 +/- 5.43 pg/ml; P<0.001]. Interestingly, in patients with liver cirrhosis, there was a correlation between serum TPO and the platelet counts [r = 0.826, P<0.001], but the spleen index did not exhibit correlation with the platelet counts and serum TPO [r = 0.036, r = - 0.103; P>0.05 respectively]. Serum TPO levels showed a negative correlation with total bilirubin, and a positive correlation with serum albumin and prothrombin concentration [r = - 0.915, r = 0.903, r = 0.856; P< 0.001 respectively]. The stepwise regression analysis showed that the prothrombin concentration, the serum albumin and the platelet count are the more significant variables with TPO [P<0.05]. It is concluded from this study that serum thrombopoietin levels increase in patients with chronic active hepatitis C, but in patients with liver cirrhosis, serum thrombopoietin levels decrease. As the liver disease progresses serum TPO decrease more. The impaired production of thrombopoietin may contribute to the development of thrombocytopenia in advanced stage of liver disease although increased splenic sequestration of platelets in the enlarged spleen may have an additional role. Since serum TPO is associated with liver function tests it is suggested that concentration of serum TPO is, to some degree, dependent on the capacity of the liver to produce this protein. It is prudent to speculate that the substitution of recombinant TPO in patients with cirrhosis will alleviate, if not cure, the thrombocytopenia observed in cirrhosis of the liver. Even more important, substitution of recombinant TPO could prevent bleeding complications by reducing the duration and extent of the platelet nadir after orthotopic liver transplantation