Gou Murohisa

Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis

OBJECTIVES:Thrombocytopenia is a common manifestation of cirrhosis. The aim of this study was to examine the relationship between serum thrombopoietin concentrations, circulating platelet levels, and the stage of hepatic fibrosis in patients with chronic viral hepatitis.METHODS:The study included 48 patients with chronic viral hepatitis (14 with stage 1 fibrosis; five with stage 2 fibrosis; three with stage 3 fibrosis; 26 with cirrhosis) and 30 healthy volunteers. Serum thrombopoietin levels were measured using an enzyme-linked immunosorbent assay. Spleen size, platelet counts, and prothrombin time were measured.RESULTS:Thrombopoietin levels of patients with fibrosis stage 1 (2.50 ± 1.60 fmol/ml) or stage 2 (1.89 ± 0.65) were significantly higher than those in patients with cirrhosis (1.21 ± 0.55) or healthy volunteers (1.26 ± 0.74). Mean platelet counts of patients with cirrhosis (8.0 ± 4.6 × 104/μl) were significantly lower than those with fibrosis stage 1 (18.6 ± 3.9) or stage 2 (16.0 ± 5.8), or healthy volunteers (24.5 ± 7.3). Patients with cirrhosis had larger spleens (30.9 ± 18.4 cm2) than those with fibrosis stage 1 (18.2 ± 6.4). Platelet counts showed a significant inverse relationship to spleen size (ρ=−0.51, p < 0.0005) and a significant positive relationship with thrombopoietin levels (ρ= 0.34, p < 0.02). Thrombopoietin levels were significantly correlated to prothrombin time (ρ= 0.45, p < 0.005).CONCLUSIONS:Serum thrombopoietin levels are elevated in patients with an early stage of chronic viral hepatitis. As the disease progresses from mild fibrosis to cirrhosis, decreased production of thrombopoietin may contribute to the further development of thrombocytopenia in cirrhosis.

Failure to respond to interferon-alpha 2a therapy is associated with increased hepatic iron levels in patients with chronic hepatitis C.

ABSTRACTRecent reports suggest the hepatic iron concentration (HIC) may influence the activity of hepatitis and the response to interferon (IFN) therapy in patients with chronic hepatitis C (CH-C). We have evaluated iron status in 28 patients with CH-C and determined if pretreatment iron status can predict the response to IFN-α therapy in these patients. Increased serum iron, transferrin saturation, and ferritin levels were observed in 3 (11%), 11 (39%), and 5 (18%) patients, respectively. Hepatic iron deposits were histologically detected in 17 (61%) patients, and 14 of them had stainable hepatocytic iron. However, all HIC values were within the normal range (203–1279 μg/g). Seven of 17 patients treated with IFN-α for 6 mo had normalization of serum transaminases and disappearance of serum HCV-RNA (responders). Nonresponders had a significantly higher median HIC compared with responders (710 vs 343 μg/g, respectively;p < 0.05). There was no significant difference in other pretreatment iron parameters, serum HCV-RNA level, or HCV-genotype between responders and nonresponders. In conclusion, mild hepatic iron accumulation occurs in patients with CH-C. Increased hepatic iron stores are associated with poor response to IFN therapy. Pretreatment HIC may be an additional host-specific parameter with a predictive value for responsiveness to IFN therapy, in addition to well-known predictive viral factors.