BioLiveScale est une entreprise privée qui propose des prestations de service de calcul de score dans le domaine du diagnostic de la sévérité des maladies du foie. Le calcul de ces scores s'appuie sur un traitement informatique de résultats biologiques sanguins usuels.

Les prestations mise en œuvre sont directement issues des travaux de recherche de l'équipe du Professeur Paul Calès responsable du service d'Hépato-Gastroentérologie du CHU d'Angers et le laboratoire HIFIH, UPRES EA 3859 de l'Université d'Angers.

Le laboratoire HIFIH (Hémodynamique, Interaction Fibrose et Invasivité tumorale Hépatique), a été créé en 1992. Il a été labellisé d'emblée " jeune équipe " puis UPRES EA par fusion avec l'équipe du Pr JL Saumet en 1996 et de façon autonome en 2004. Il fait partie de l'IFR 132 de l'Université d'Angers.


L'équipe comporte 27 membres dont 8 avec l'HDR.

Il regroupe les axes suivants :


Hypertension portale : F. Oberti,
Fibrose hépatique et carcinome hépatocellulaire : P. Calès (directeur),
Hémodynamique splanchnique et choc septique : P. Asfar,
Virus des hépatites : F. Lunel,
Endoscopie digestive interventionnelle : J. Boyer.


Tous ces thèmes sont interconnectés entre eux. L'interdisciplinarité qui associe hépatologie, gastroentérologie, virologie, anatomo-pathologie, histologie, biochimie, réanimation, chirurgie viscérale est aussi reflétée par une continuité entre recherche pré-clinique et clinique sur le site mais aussi en dehors.

A titre d'exemple, nous avons testé, en tant qu'investigateur principal, le vapréotide, analogue retard de la somatostatine, développé par une société suisse, au laboratoire puis dans un essai clinique multicentrique publié dans le NEJM faisant l'objet d'une procédure internationale d'enregistrement de médicament.

Paul CALES, Service d'Hépato-Gastroentérologie, CHU, 49033 Angers Cedex 01, France.

5 principales publications du directeur du laboratoire

1 - Pascal J, Calès P, and a Multicenter Study Group. Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med 1987; 317:856-61.

2 - Poynard T, Calès P, Pasta L, Ideo G, Pascal J, Pagliaro L et al. Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. N Engl J Med 1991; 324:1532-8.

3 - Calès P, Masliah C, Bernard B, Garnier PP, Silvain S, Szostak-Talbodec N, et al. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med 2001;344:23-8.

4 - Calès P, Zabotto B, Meskens C, Caucanas J, Vinel J, Fermanian J et al. Gastro-esophageal endoscopic features in cirrhosis : observer variability, interassociations and relationship to hepatic dysfunction. Gastroenterology 1990; 98:156-62.

5 - Calès P, Oberti F, Veal N, Fort J , Kaassis M, Moal F et al. Splenorenal shunt blood flow by transit-time ultrasound as an index of collateral circulation in portal hypertensive rats. Hepatology 1998; 28:1269-74.

Principales publications du laboratoire

Fort J, Oberti F, Pilette C, Veal N, Gallois Y, Douay O et al, Calès P. Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats. Hepatology 1998; 28:1525-31.

Calès P, Oberti F, Veal N, Fort J, Kaassis M, Moal F et al. Splenorenal shunt blood flow by transit-time ultrasound as an index of collateral circulation in portal hypertensive rats. Hepatology 1998; 28:1269-74.

Veal N, Oberti F, Moal F, Vuillemin E, Fort J, Kaassis M et al . Spleno-renal shunt blood flow is an accurate index of collateral circulation in different models of portal hypertension and after pharmacological changes in rats. J Hepatol 2000; 32:434-40

Veal N, Moal F, Wang J, Vuillemin E, Oberti F, Roy E, Kaassis M, Trouvé R, Saumet JL, Calès P. A new method of cardiac output measurement using ultrasound velocity dilution in rats. J Apl Physiol 2001;91:1274-82

Oberti F, Valsesia E, Pilette C, Rousselet M, Bedossa P, Aubé C et al, Calès P. Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology 1997;113:1609-16.

Calès P, Masliah C, Bernard B, Garnier PP, Silvain S, Szostak-Talbodec N, et al. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med 2001;344:23-8.

Croquet V, Moal F, Veal N, Wang J, Oberti F, Roux J, Vuillemin E, Gallois Y, Douay O, Chappard D, Calès P. Hemodynamic and antifibrotic effects of the chronic administration of losartan in rats with portal hypertension and liver fibrosis. J Hepatol 2002;37:773-80.

Moal F, Chappard D, Wang J, Vuillemin E, Michalak-Provost S, Marie Christine Rousselet MC, Oberti F, Calès P. Fractal dimension can distinguish models and pharmacological changes in liver fibrosis in rats. Hepatology 2005;42:1373-1381.

Rousselet MC, Michalak S, Dupré F, Croué A, Bedossa P, Saint-André JP, Calès P and Hepatitis network 49. Sources of variability in histological scoring of chronic viral hepatitis. Hepatology 2005;41:257-64.

"Fibrose du foie "

1 - Oberti F, Pilette C, Rifflet H, Maïga M, Moreau A, Gallois Y et al, Calès P. Effects of simvastatin, pentoxifylline and spironolactone on hepatic fibrosis and portal hypertension in rats with bile duct ligation. J Hepatol 1997; 26:1363-71.

2 - Oberti F, Valsesia E, Pilette C, Rousselet M, Bedossa P, Aubé C et al, Calès P. Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology 1997;113:1609-16.

3 - Fort J, Oberti F, Pilette C, Veal N, Gallois Y, Douay O et al, Calès P. Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats. Hepatology 1998; 28:1525-31.

4 - Pilette C, Rousselet M, Bedossa P, Chappard D, Oberti F, Rifflet H et al, Calès P. Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores : comparison with serum markers. J Hepatol 1998; 28:439-46.

5 - Fort J, Pilette C, Veal N, Oberti F, Gallois Y, Douay O et al, Calès P. Effects of long-term administration of interferon in two models of liver fibrosis in rats. J Hepatol 1998; 29:263-70.

6 - Fort J, Pilette C, Oberti F, Veal N, Gallois Y, Douay O et al, Calès P. Long-term administration of PGE1 increases liver fibrosis and collateral blood flow in bile-duct-ligated rats. J Hepatol 1999; 30:70-6.

7 - Aubé C, Oberti F, Korali N, Korali N, Namour A, L et al, Calès P. Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis. J Hepatol 1999; 30:472-8.

8 - Croquet V, Vuillemin E, Ternisien C, Pilette C, Oberti F, Gallois Y, Trossaert M, Rousselet MC, Chappard D, Calès P. Prothrombin index is an indirect marker of severe liver fibrosis. Eur J Gastroenterol Hepatol 2002;14: 1133-41.

9 - Moal F, Chappard D, Wang J, Vuillemin E, Michalak-Provost S, Marie Christine Rousselet MC, Oberti F, Calès P. Fractal dimension can distinguish models and pharmacological changes in liver fibrosis in rats. Hepatology 2002;36:840-9.

10 - Croquet V, Moal F, Veal N, Wang J, Oberti F, Roux J, Vuillemin E, Gallois Y, Douay O, Chappard D, Calès P. Hemodynamic and antifibrotic effects of the chronic administration of losartan in rats with portal hypertension and liver fibrosis. J Hepatol 2002;37:773-80.

11- Michalak S, Rousselet MC, Bedossa P, Pilette C, Chappard D, Oberti F, Gallois Y, Calès P. Respective role of porto-septal fibrosis and centrolobular fibrosis in alcoholic liver diseases. J Pathol 2003;201:55-62.

12 - Aubé C, Winkfield B, Oberti F, Vuillemin E, Rousselet MCR, Caron C, Calès P. New US-Doppler signs improve the non-invasive diagnosis of cirrhosis or severe liver fibrosis. Eur J Gastroenterol Hepatol 2004;16:743-51.

13 - Aubé C, Racineux PX, Lebigot J, Oberti F, Croquet V, Argaud C, Cales P, Caron C. Diagnosis and quantification of hepatic fibrosis with diffusion weighted MR imaging: preliminary results. J Radiol 2004;85:301-6.

14 - Rousselet MC, Michalak S, Dupré F, Croué A, Bedossa P, Saint-André JP, Calès P and Hepatitis network 49. Sources of variability in histological scoring of chronic viral hepatitis. Hepatology 2005;41:257-64.

15 - Calès P, Oberti F, Michalak S, Hubert-Fouchard I, Rousselet MC, Konaté A, Gallois Y, Ternisien C, Chevailler A, Lunel F. A novel panel of serum markers to assess the degree of liver fibrosis. Hepatology 2005; 42:1373-81.

"Hypertension portale : essais cliniques"

16 - Pascal J, Calès P, and a Multicenter Study Group. Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med 1987; 317:856-61.

17 - Calès P, Lacaine F, Bleichner G, Valla D, Lamouliatte H, Belghiti J et al. The emergency treatment of upper gastrointestinal bleeding due to portal hypertension in cirrhotic patients. Report on a french consensus meeting. Eur J Gastroenterol Hepatol 1991; 3:413-8.

18 - Rossi V, Calès P, Burtin P, Person B, Charneau J, Pujol P et al. Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy. J Hepatol 1991; 12:283-9.

19 - Poynard T, Calès P, Pasta L, Ideo G, Pascal J, Pagliaro L et al. Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. N Engl J Med 1991; 324:1532-8.

20 - Vinel J, Lamouliatte H, Calès P, Combis J, Roux D, Desmorat H et al. Propranolol reduces the rebleeding rate during endoscopic sclerotherapy before variceal obliteration. Gastroenterology 1992; 102:1760-3.

21 - Calès P, and the Study Group of Primary Prophylaxis. Factors associated with the failure of propranolol for the prevention of first bleeding in cirrhotic patients. Gastroenterol Clin Biol 1992; 16:504-10.

22 - Besson I, Ingrand P, Person B, Boutroux D, Heresbach D, Bernard P, Hochain P, Larricq J, Gourlaouen A, Ribard D, et al. Sclerotherapy with or without octreotide for acute variceal bleeding. N Engl J Med 1995;333:555-60.

23 - Calès P, Oberti F, Payen JL, Naveau S, Guyader D, Blanc P, et al. Lack of effect of propranolol in the prevention of large esophageal varices in patients with cirrhosis: a randomized trial. Eur J Gastroenterol Hepatol 1999; 11:741-5.

24 - Calès P, Lacave N, Silvain C, Vinel JP, Besseghir K, Lebrec D. Prospective study on the application of the Baveno II consensus conference criteria in patients with cirrhosis and gastrointestinal bleeding. J Hepatol 2000;33:738-41.

25 - Escorsell A, Del Arbol LR, Planas R, Albillos A, Banares R, Calès P, Pateron D, Bernard B, Vinel JP, Bosch J, Test Study Members. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology 2000;32:471-6.

26 - Calès P, Masliah C, Bernard B, Garnier PP, Silvain S, Szostak-Talbodec N, et al. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med 2001;344:23-8.

27 - Bosch J, Thabut D, Bendtsen F, D'Amico G, Albillos A, Gonzalez Abraldes J, Fabricius S, Erhardtsen E, de Franchis R; European Study Group on rFVIIa in UGI Haemorrhage. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004;127:1123-30.

Publications "Hypertension portale : études pharmacologiques "

28 - Calès P, Braillon A, Jiron M, Lebrec D. Superior portosystemic collateral circulation estimated by azygos blood flow in patients with cirrhosis, lack of correlation with oesophageal varices and gastrointestinal bleeding. Effect of propranolol. J Hepatol 1984; 1:37 -46.

29 - Calès P, Braillon A, Girod C, Lebrec D. Acute effects of propranolol on splanchnic circulation in normal and portal hypertensive rats. J Hepatol 1985; 1:349-57.

30 - Braillon A, Jiron M, Valla D, Calès P, Lebrec D. Effect of propranolol on hepatic blood flow in patients with cirrhosis. Clin Pharmacol Ther 1985; 37:376-80.

31 - Braillon A, Calès P, Lebrec D. Comparison of the acute effects of mepindolol and propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis. Int J Clin Pharmacol Res 1985; 4:223-8.

32 - Braillon A, Calès P, Girod C, Lebrec D. Alterations in response of the portal tributary vascular bed to the B-agonist dobutamine in rats with extrahepatic portal hypertension. J Hepatol 1986; 2:267-75.

33 - Braillon A, Calès P, Valla D, Gaudy D, Geoffroy P, Lebrec D. Influence of the degree of liver failure on systemic and spanchnic haemodynamics and on response to propranolol in patients with cirrhosis. Gut 1986; 27:1204-9.

34 - Vinel J, Caucanas J, Calès P, Suduca J, Voigt J, Pascal J. Effect of propranolol on metabolic activity of the liver in patients with alcoholic cirrhosis. J Hepatol 1988; 7:186-92.

35 - Vinel J, Caucanas J, Combis J, Calès P, Voigt J, Pascal J. Verapamil has no effect on porto-hepatic pressure gradient, hepatic blood flow and elimination function of the liver in patients with liver cirrhosis. J Hepatol 1989; 8:302-7.

36 -Calès P, Pierre-Nicolas M, Guell A, Mauroux J, Franco-Sempe A, Vinel J et al. Propranolol does not alter cerebral blood flow and functions in cirrhotic patients without previous hepatic encephalopathy. Hepatology 1989; 9:439-42.

37 - Calès P, Grasset D, Ravaud A, Meskens C, Blanc M, Vinel J et al. Pharmacodynamic and pharmacokinetic study of propranolol in patients with cirrhosis and portal hypertension. Br J Clin Pharmacol 1989; 27:763-70.

38 - Vinel J, Denoyel P, Viossat I, Calès P, Caucanas J, Chabrier P et al . Atrial natriuretic peptide, plasma renin activity, plasma volume, systemic vascular resistances, and cardiac output in patients with cirrhosis. J Gastroenterol Hepatol 1989; 4:529-35.

39 - Vinel J, Monin J, Combis J, Calès P, Desmorat H, Pascal J. Haemodynamic evaluation of molsidomine, a vasodilatator with antianginal properties in patients with alcoholic cirrhosis. Hepatology 1990; 11:239-42.

40 - Desmorat H, Vinel J, Lahlou O, Pipy B, Badia P, Calès P et al. Systemic and splanchnic hemodynamic effects of molsidomine in rats with carbon tetrachloride-induced cirrhosis. Hepatology 1991; 13:1181-4.

41 - Calès P, Caillau H, Crambes O, Vinel J, Desmorat H, Rocher I et al. Hemodynamic and pharmacokinetic study of tertatolol in patients with alcoholic cirrhosis and portal hypertension. J Hepatol 1993; 19:43 -50.

42 -Oberti F, Rifflet H, Maïga M, Pilette C, Gallois Y, Douay O et al, Calès P. Prevention of portal hypertension by propranolol and spironolactone in rats with bile duct ligation. J Hepatol 1997; 26:167-73.

43 - Moreau R, Oberti F, Lahaye P, Gadano A, Cailmail S, Sogni P et al , Calès P. In vitro and in vivo vascular responses to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis. J Gastroenterol Hepatol 1998; 13:1254-8.

44 - Oberti F, Veal N, Kaassis M, Pilette C, Rifflet H, Trouvé R, Calès P. Hemodynamic effects of terlipressin and octreotide administration alone or in combination in portal hypertensive rats. J. Hepatol 1998;29:103-111.

45 - Pateron, D, Oberti, F, Lefilliatre, P, Veal, N, Tazi, KA, Sogni, P, Poirel, O, Heller, J, Moreau, R, Calès, P, and Lebrec, D. Relationship between vascular reactivity in vitro and blood flows in rats with cirrhosis. Clin Sci 1999;97:313-8.

46 - Veal N, Oberti F, Moal F, Vuillemin E, Fort J, Kaassis M et al. Spleno-renal shunt blood flow is an accurate index of collateral circulation in different models of portal hypertension and after pharmacological changes in rats. J Hepatol 2000; 32:434-40.

47 - Veal N, Moal F, Oberti F, Vuillemin E, Calès P. Hemodynamic effects of acute and chronic administration of vapreotide in rats with cirrhosis. Dig Dis Sci 2003;48:115-8.

48 - P Asfar, M Pierrot, N Veal, F Moal, F Oberti, V Croquet, O Douay, Y Gallois, JL Saumet, P Alquier, P Calès. Low dose terlipressin improves systemic and splanchnic hemodynamics in fluid challenged endotoxic rats. Crit Care Med 2003;31;215-20.

"Hypertension portale : Région gastrointestinale "

49 - Calès P, Desmorat H, Vinel J, Caucanas J, Ravaud A, Gerin P et al. Incidence of large esophageal varices in patients with cirrhosis. Application to prophylaxis of first bleeding. Gut 1990; 31:1298-302.

50 - Calès P, Zabotto B, Meskens C, Caucanas J, Vinel J, Fermanian J et al. Gastro-esophageal endoscopic features in cirrhosis : observer variability, interassociations and relationship to hepatic dysfunction. Gastroenterology 1990; 98:156-62.

51 - Calès P, Burtin P, Person B, Ruget O, Charlois T, Ferrero P et al. Interobserver agreement on endoscopic diagnosis of diffuse gastric mucosal features in cirrhotic patients. Eur J Gastroenterol Hepatol 1993; 5:263-8.

52 - Payen J, Calès P, Pienkowski P, Sozzani P, Kervran A, Frexinos J et al. Weakness of mucosal barrier in portal hypertensive gastropathy of alcoholic cirrhosis. Effect of propranolol and enprostil. J Hepatol 1995; 23:689-96.

53 - Payen J, Calès P, Voigt J, Barbe S, Pilette C, Dubuisson L et al. Severe portal hypertensive gastropathy and antral vascular ectasia are distinct entities in patients with cirrhosis. Gastroenterology 1995; 108:138-44.

54 - Charneau J, Petit R, Calès P, Dauver A, Boyer J. Antral motility in patients with cirrhosis with or without antral vasculare ectasia. Gut 1995; 37:488-92.

55 - Burtin P, Calès P, Oberti F, Joundy N, Person B, Carpentier S et al. Endoscopic ultrasonographic signs of portal hypertension in cirrhosis. Gastrointest Endosc 1996; 44:257-61.

56 - Oberti F, Burtin P, Maïga M, Valsesia E, Pilette C, Calès P. : Gastroesophageal endoscopic signs of cirrhosis: independent diagnostic accuracy, interassociation, and relationship to etiology and hepatic dysfunction. Gastrointest Endosc 1998; 48:148-57.

57 - Oberti F, Maïga M, Veal N, Fort J, Kaassis M, Moal F et al, Calès P. Measurement of collateral circulation blood flow in anesthetized portal hypertensive rats. Gastroenterol Clin Biol 1998;22:697-704.

58 - Calès P, Oberti F, Veal N, Fort J, Kaassis M, Moal F et al. Splenorenal shunt blood flow by transit-time ultrasound as an index of collateral circulation in portal hypertensive rats. Hepatology 1998; 28:1269-74.

59 - Pilette C, Oberti F, Aubé C, Rousselet M, Bedossa P, Gallois Y et al . Non-invasive diagnosis of esophageal varices in chronic liver diseases. J Hepatol 1999; 31:867-73.

60 - Calès P, Oberti F, Delmotte JS, Baslé M, Casa C, Arnaud JP. Gastric mucosal surface in cirrhosis evaluated by magnifying endoscopy and scanning electronic microscopy. Endoscopy 2000;32:614-23.

61 - Veal N, Auduberteau H, Lemarié C, Oberti F, Calès P. Effects of octreotide on intestinal transit and bacterial translocation in conscious rats with portal hypertension and liver fibrosis. Dig Dis Sci 2001;46:2367-73.

62 - Calès P Oberti F, Bernard-Chabert B, Payen JL. Evaluation of Baveno recommendations for grading esophageal varices. J Hepatol 2003;39:657-9.

63 - Winkfield B, Aubé C, Burtin P, Calès P. Inter- and intra-observer variability in Hepatology. Eur J Gastroenterol Hepatol 2003;15:959-66.