Anna Kreil

Serum Level of IP-10 Increases Predictive Value of IL28B Polymorphisms for Spontaneous Clearance of Acute HCV Infection

BACKGROUND & AIMS Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC). METHODS We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC. RESULTS Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [113-2470] pg/mL) than those without spontaneous clearance (1481 [141-4412] pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P < .01). CONCLUSIONS The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.

Characterization of 123I-vascular endothelial growth factor–binding sites expressed on human tumour cells: Possible implication for tumour scintigraphy

To explore the possibility of vascular endothelial growth factor (VEGF) receptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of 123I‐labelled VEGF165 (123I‐VEGF165) and 123I‐VEGF121 to human umbilical vein endothelial cells (HUVECs), several human tumour cell lines (HMC‐1, A431, KU812, U937, HEP‐1, HEP‐G2, HEP‐3B and Raji), a variety of primary human tumours (n = 40) and some adjacent non‐neoplastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high‐affinity 123I‐VEGF165‐binding site were found on the cell surface of HUVECs. In contrast, one class of high‐affinity binding sites for 123I‐VEGF165 was found on HMC‐1, A431, HEP‐1, HEP‐G2, HEP‐3B and U937 cells as well as many primary tumours. For 123I‐VEGF121, a single class of high‐affinity binding site was found on certain cell lines (HUVEC, HEP‐1 and HMC‐1) and distinct primary tumours (primary melanomas, ductal breast cancers and ovarian carcinomas as well as meningiomas). Tumour cells expressed significantly higher numbers of VEGF receptors compared with normal peripheral blood cells and adjacent non‐neoplastic tissues. Immunohistochemical staining revealed that the VEGF receptor Flk‐1 is expressed to a much higher extent within malignant tissues compared with neighbouring non‐neoplastic cells. We observed significantly greater specific binding of 123I‐VEGF165 and 123I‐VEGF121 to a variety of human tumour cells/tissues compared with the corresponding normal tissues or normal peripheral blood cells. In comparison with 123I‐VEGF121, 123I‐VEGF165 bound to a higher number of different tumour cell types with a higher capacity. Thus, 123I‐VEGF165 may be a potentially useful tracer for in vivo imaging of solid tumours.

Thrombopoietin in Plasmodium falciparum malaria.

Thrombopoietin (TPO) is the key growth factor for platelet production and is elevated in states of platelet depletion. As thrombocytopenia is a common finding in malaria, we analysed TPO regulation before, during and after antimalarial treatment. Before treatment, TPO serum levels were significantly higher in patients with severe malaria (n = 35) than in patients with uncomplicated malaria (n = 44; P = 0·024), normalizing within 14–21 d of therapy. The rapid normalization of TPO levels and increase in low peripheral platelet counts after treatment indicate that the biosynthesis of TPO and its regulation in malaria patients are normal.

1320 IL28B POLYMORPHISMS AND IP-10 ARE ASSOCIATED WITH ACUTE PRESENTATION AND SPONTANEOUS CLEARANCE IN RECENT HEPATITIS C VIRUS INFECTION

prevalence and potential effect of graft vs recipient IL28B genotype on early HCV-RNA kinetics after liver transplantation (LT). Objective and Methods: Retrospective-prospective assessment of IL28B-SNP rs12979860 by PCR-RFLP (Forward – TTATCGCATACGGCTAGGC; Reverse – ACAATTCCCACCACGAGAC; BstUI) in a cohort of HCV subjects undergoing LT between Jan 2001-November 2010, and evaluation of the impact of graft vs recipient IL28B genotypes on week 4 HCV-RNA decay. Results: IL28B was performed in 89/171 consecutive HCV-LT subjects (52%): both graft/recipient 55 (62%), only recipient 17 (19%), only graft 17 (19%), 77 HCV G1/4 (86.5%). The overall distribution of IL28B genotypes in graft (n = 72) was: C/C 38% (n =27), C/T 54% (n =39), T/T 8% (n =6), and in recipients (n = 72): C/C 33% (n =24), C/T 46% (n =33), T/T 21% (n =15). When both samples were available (n = 55), concordance was observed in 26 (47%): C/C 47%, C/T 58%, T/T 25%), with no differences according to HCV genotype (56% G2/G3, 46% G1/G4, p = 0.72). 61 patients (36%) started peg-IFN/RBV after LT, 54 HCV-G1/4 (88.5%), with median HCV-RNA 6.9 log10 IU/ml (5.15–8.3), and IL28B available in 60 (98%): both samples 38 (63%), graft 13 (22%), recipient 9 (15%). In HCV G1/4 subjects, HCV-RNA decay at week 4 was strongly influenced by recipient (C/C −1.85 log10 IU/ml vs C/T −0.95 log10 IU/ml and T/T −0.76 log10 IU/ml, P = 0.053; C/C −1.85 log10 IU/ml vs nonC/C −0.88 log10 IU/ml p =0.017), but not by graft IL28B genotype (C/C −1.05 log10 IU/ml, C/T −1.11 log10 IU/ml, T/T −0.09 log10 IU/ml, P = 0.31; C/C −1.21 log10 IU/ml vs non-C/C −0.93 log10 IU/ml p =0.4), effect not observed in HCV G2/3 subjects: graft (p = 0.37), recipient (p = 0.55). Conclusions: In LT subjects, C/T was the most prevalent IL28B genotype, both in graft and recipients, with a high concordance rate. Only in patients with HCV G1/4, recipient but not graft IL28B genotype significantly affected week 4 HCV-RNA decay on pegIFN/RBV.