Joël Fort

Effects of long-term administration of interferon α in two models of liver fibrosis in rats

Abstract Background/Aims: The aim of this study was to assess the effect of the early and chronic administration of interferon α in the prevention of hepatic fibrosis and portal hypertension. Methods: Rats with liver fibrosis due to bile duct ligation or CCl 4 were divided into three groups: sham, placebo and interferon α 2a 100 000 UI/day. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and mRNA (fibronectin, procollagen α2(I)) contents, and serum hyaluronate. Systemic and splanchnic hemodynamics were also evaluated. Results: Interferon α significantly decreased fibrosis in the CCl 4 model only: area of fibrosis: 13.9±3.7 vs 10.5±3.3% ( p p r =0.77 in the biliary model and r =0.87 in the CCl 4 model, p p 4 model. No significant effects were observed in rats with biliary fibrosis. Conclusions: The early and chronic administration of interferon α prevents the development of liver fibrosis and porto-collateral circulation in the CCl 4 model but not in the biliary model. However, the antifibrotic effects of interferon need to be confirmed in further studies.

Interobserver agreement on endoscopic diagnosis of bleeding peptic ulcers

BACKGROUND The aim of this prospective study was to evaluate the interobserver agreement of stigmata of recent hemorrhage of bleeding peptic ulcers. METHODS Sixty-one consecutive adult patients were enrolled in the study and nine (three junior and six senior) endoscopists reviewed standardized video recordings of endoscopic examinations. Interobserver agreement was evaluated using the kappa (kappa) index, intraclass correlation coefficient, and proportion of agreement. Observer bias and poorly trained observers were investigated. RESULTS Interobserver agreement was very good for oozing (kappa = 0.68), good for clot (kappa = 0.51), poor for spurting (kappa = 0.29) and visible vessels (kappa = 0.33), and excellent for the absence of stigmata (kappa = 0.82). Observer bias sometimes occurred and the number of poorly trained observers was low. The kappa indexes were significantly better in senior than in junior investigators: 0.48 +/- 0.16 versus 0.37 +/- 0.26, respectively, p < 0.05. The agreement between the in vivo evaluation and video tape recordings (intraobserver agreement) was good (kappa = 0.60 +/- 0.19). There was no training phenomenon between the first and the second half of the patient group. CONCLUSIONS The endoscopic classification of bleeding ulcers might be simplified by limiting grading to a few classes. Special attention should be paid to the training of endoscopists.

Spleno-renal shunt blood flow is an accurate index of collateral circulation in different models of portal hypertension and after pharmacological changes in rats

BACKGROUND/AIMS Recently, we developed a new method to measure collateral blood flow in rats: splenorenal shunt (SRS) blood flow (BF). The aims were to evaluate the reproducibility of SRSBF measurement in different models of portal hypertension, and to investigate the ability of SRSBF to disclose pharmacological changes. METHODS Hemodynamics were determined in anesthetized rats with secondary biliary, CCl4 or DMNA cirrhosis and portal vein ligation (PVL) under baseline and pharmacological (octreotide, vapreotide) conditions. The main measurements performed were: SRSBF by the transit time ultrasound (TTU) method and % portosystemic shunts (PSS) by the microsphere method. RESULTS SRSBF was 6 to 10 times higher in portal hypertensive rats and was similar in the different models of cirrhosis but was higher in portal vein ligated rats than in cirrhotic rats (1.1+/-0.7 vs 0.6+/-0.7 ml x min(-1) x 100 g(-1), p=0.01). SRSBF was correlated with mesenteric %PSS (r=0.61, p<0.01), splenic %PSS (r=0.54, p<0.05), portal pressure (r= 0.32, p<0.05) and the area of liver fibrosis (r=0.33, p<0.05). Octreotide significantly decreased SRSBF (-23+/-20%, p<0.01 vs placebo: -6+/-8%, NS). Vapreotide significantly decreased SRSBF but not mesenteric or splenic %PSS compared to placebo. The variations in SRSBF (-26+/-32%) and in splenic %PSS (0+/-15%) with vapreotide were significantly different (p<0.05) and not correlated (r=-0.1, NS). CONCLUSIONS Determination of SRSBF by TTU is an accurate way to measure collateral blood flow in different models of intra- and extra-hepatic portal hypertension in rats. Its sensitivity provides accurate measurement of pharmacological changes, unlike the traditional estimation of %PSS by the microsphere method.

Long-term administration of PGE1 increases liver fibrosis and collateral blood flow in bile-duct-ligated rats

BACKGROUND/AIMS The aim of this study was to assess the effect of early and chronic administration of a prostaglandin E1 analogue (misoprostol) in the prevention of liver fibrosis and portal hypertension. METHODS Liver fibrosis was induced by bile duct ligation. Controls had a sham operation. Bile-duct-ligated rats were divided into two groups: placebo (vehicle only) and misoprostol (10 microg/d by gavage) for 4 weeks after surgery. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline content and serum hyaluronate. Systemic and splanchnic hemodynamics were evaluated including spleno-renal shunt blood flow by the transit-time ultrasound technique. RESULTS Mean arterial pressure was significantly lower in the misoprostol group (p<0.01). There was an unexpected increase in fibrosis parameters in the misoprostol group compared to the placebo group, e.g. area of fibrosis: 9.5+/-4.0 vs 15.0+/-8.1% (p<0.05). Spleno-renal shunt blood flow was significantly higher in the misoprostol group than in the placebo group (4.6+/-3.7 vs 2.2+/-2.0 ml/min, p<0.05) while portal pressure was unchanged. CONCLUSIONS The early and chronic administration of misoprostol enhances porto-collateral circulation blood flow and the development of liver fibrosis in bile-duct-ligated rats.