Early anemia and rapid virological response improve the predictive efficiency of IL28B-genotype for treatment outcome to antiviral combination therapy in patients infected with chronic HCV genotype 1.

IL28B genotypes and virological response within 4 weeks are predictors of sustained virological response in patients infected with chronic hepatitis C virus (HCV) genotype 1 treated with antiviral dual combination therapy. The predictive value of "early" anemia (within 4 weeks) alone or in combination with the two other predictors has not been studied yet. A total of 305 pegylated interferon-α and ribavirin-treated patients with HCV genotype 1 were included in this study. Hemoglobin values at week 0, 4, 8, and 12 as well as the predictive efficiency of early anemia (hemoglobin value below the gender-specific lower limit: female < 11.5; male < 13.5 g/dl) during therapy were assessed with IL28B genotypes and rapid virological response. Forty-eight percent of treated patients developed early anemia. In both females and males (64%), a decrease of hemoglobin concentration of 3 g/dl (female: 14.7 ± 1.1 to 11.4 ± 1.3; male: 15.2 ± 1.2 to 12.2 ± 1.5) significantly correlated with sustained virological response. 64% of IL28B-CC patients showed a sustained virological response. Seventy-eight percent of patients with rapid virological response definitively eliminated the virus. Early anemia (81:48:41%) and rapid virological response (83:91:92%) increased the predictive efficiency of IL28B rs12979860 genotype distribution (CC:CT:TT). IL28B-CC and early anemia as well as IL28B-CC and rapid virological response had an Odds ratio of 42.4 or 75 to achieve a sustained virological response compared to TT without early anemia or rapid virological response. This finding may help to early identify responders to standard PEG-IFN-α and ribavirin treatment even within those with unfavorable IL28B genotype.

Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-gamma and IFN-alpha is reversed by TGF-beta in sinusoidal endothelial cells and hepatic mononuclear phagocytes.

BACKGROUND AND AIM: The mechanisms of transmigration of inflammatory cells through the sinusoids are still poorly understood. This study aims to identify in vitro conditions (cytokine treatment) which may allow a better understanding of the changes in PECAM (platelet endothelial cell adhesion molecule)-1-gene-expression observed in vivo. METHODS AND RESULTS: In this study we show by immunohistochemistry, that there is an accumulation of ICAM-1 (intercellular cell adhesion molecule-1) and ED1 positive cells in necrotic areas of livers of CCl4-treated rats, whereas there are few PECAM-1 positive cells observable. After the administration of CCl4, we could detect an early rise of levels of IFN-gamma followed by an enhanced TGF-beta protein level. As shown by Northern blot analysis and surface protein expression analysed by flow cytometry, IFN-gamma-treatment decreased PECAM-1-gene-expression in isolated SECs (sinusoidal endothelial cells) and mononuclear phagocytes (MNPs) in parallel with an increase in ICAM-1-gene-expression in a dose and time dependent manner. In contrast, TGF-beta-treatment increased PECAM-1-expression. Additional administration of IFN-gamma to CCl4-treated rats and observations in IFN-gamma-/- mice confirmed the effect of IFN-gamma on PECAM-1 and ICAM-1-expression observed in vitro and increased the number of ED1-expressing cells 12 h after administration of the toxin. CONCLUSION: The early decrease of PECAM-1-expression and the parallel increase of ICAM-1-expression following CCl4-treatment is induced by elevated levels of IFN-gamma in livers and may facilitate adhesion and transmigration of inflammatory cells. The up-regulation of PECAM-1-expression in SECs and MNPs after TGF-beta-treatment suggests the involvement of PECAM-1 during the recovery after liver damage.

Colorectal tumors with complete obstruction--endoscopic recovery of passage replacing emergency surgery? A report of two cases.

BACKGROUND: Incomplete or complete obstructive ileus due to colorectal cancer is generally treated by emergency surgery that has higher morbidity and mortality than elective surgery. CASE PRESENTATION: Here we describe an endoscopic technique by which a safe bowel decompression was performed instead of emergency surgery in two patients with complete tumorous obstruction of the colon. By means of a polypectomy snare, a soft wire, an ERCP catheter, a set of endoscopes with different diameters (baby endoscope, gastroscope) and of argon plasma coagulation the tumor mass was reduced and the tumor stenosis was passed. The patients recovered from symptoms of colon obstruction, no procedure-associated complications were observed. One patient had surgery of the sigmoid tumor one week later (UICC-stage III), the other patient (UICC-stage IV) received systemic chemotherapy starting one week after endoscopic decompression. CONCLUSION: Complete tumorous obstruction of the colon may be managed by endoscopic tumor debulking avoiding high risk emergency surgery and allowing immediate medical treatment of the primary tumor and of metastases.

Gelsolin gene expression is upregulated in damaged rat and human livers within non-parenchymal cells and not in hepatocytes.

Gelsolin, a 90-kDa protein, was suggested to be involved in cell motility, to inhibit apoptosis and to have a protective role for tissue. This study intends to analyse the modulation of cytoplasmic gelsolin expression in damaged rat and human livers and to identify its cellular sources. In the normal liver gelsolin-immunoreactive cells could be identified along vessel walls and along the sinusoids. In cultured rat hepatic stellate cells (HSCs), liver myofibroblasts (MFs), mononuclear cells (MCs) and sinusoidal endothelial cells (SECs), but not in hepatocytes, gelsolin expression could be detected by immunostaining and Northern blot analysis. In acute CCl4-induced liver damage there was no gelsolin positivity detectable in necrotic areas. However, in human fulminant hepatic failure positivity in the necrotic areas was detected. In chronically damaged rat and human livers gelsolin-immunoreactive cells could be identified within the fibrotic septa. Northern blot analysis revealed an increase of the gelsolin-specific transcript level under conditions of acute and chronic human or rat liver damage. The amount of gelsolin-specific transcripts in SECs and large MCs isolated from damaged rat livers increased in comparison to cells obtained from normal rats. However, the amount of gelsolin-specific transcripts in small MCs (representing recruited inflammatory cells) decreased. In conclusion, SECs, MCs, MFs and HSCs, but not hepatocytes, express gelsolin. In the damaged liver all tested cell populations but the inflammatory cells and the hepatocytes are responsible for the enhanced gelsolin expression.