Evidence of a significant role for Fas-mediated apoptosis in HCV clearance during pegylated interferon plus ribavirin combination therapy.

BACKGROUND: The role of apoptosis in treatment-induced HCV clearance is controversial. We sought to assess the kinetics of serum apoptosis-related cytokines during pegylated interferon-α2a or -α2b plus weight-based ribavirin therapy for genotype 1 chronic HCV infection. METHODS: Serum levels of soluble Fas (sFas), soluble Fas ligand (sFasL) and soluble tumour necrosis factor receptor I (sTNF-RI) were measured at baseline, week 12 and 24 weeks after the end of therapy. RESULTS: Sustained virological response (SVR) was achieved in 46% of the 164 included patients, 29% had a non-response (NR) and 25% had relapse (RR). NR patients presented with higher levels of sFasL at baseline and lower levels of sTNF-RI at week 12 as compared to RR and SVR patients. Lower concentrations of sFas were observed in SVR patients 24 weeks after treatment as compared to RR and NR patients. An increase in sFas at week 12 followed by a significant drop 24 weeks after therapy was observed among SVR patients. An increase in sFasL during and after treatment was observed in RR and SVR patients. NR patients exhibited an earlier drop in sTNF-RI levels as compared to RR and SVR patients. CONCLUSIONS: Virological response during HCV therapy was associated with an increase of sFas and sFasL, and maintenance of increased concentrations of sTNF-RI.

Thrombopoietin serum levels do not correlate with thrombocytopenia in hepatic schistosomiasis.

BACKGROUND: In severe forms of cirrhosis reduced liver synthesis of thrombopoietin (Tpo) can contribute to thrombocytopenia. In the hepatosplenic form of schistosomiasis, portal hypertension is the most evident clinical complication, although a deficiency of protein synthesis may be detected early. Our aim was to determine, for the first time in schistosomiasis, Tpo serum concentrations in patients with chronic forms of the disease. METHOD: Twenty-four patients with the pure form of schistosomiasis were studied; 13 had the hepatosplenic form (HE, with portal hypertension) and 11 had the hepatointestinal form (HI, without portal hypertension). Patients were HBsAg, anti-HBc and anti-HCV negative, and reported alcohol ingestion below 160 g/week. RESULTS: The Tpo serum concentration, determined in 10 healthy volunteers, varied from undetectable (< 15 pg/mL) to 489 pg/mL (median 208 pg/mL). The HE and HI groups differed (p = 0.004) in regard to the prothrombin index, thrombocytemia and gamma-glutamyltransferase but not in regard to Tpo (p = 0.622). No significant correlation was found between Tpo and the other parameters (p > 0.05). CONCLUSIONS: The results suggest that Tpo serum concentration does not mirror and/or has no significant participation in the mechanisms responsible for the thrombocytopenia observed in schistosomiasis patients with splenomegaly and portal hypertension.