Vincent Croquet

Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension

BACKGROUND/AIMS To assess the effects of the early and chronic administration of losartan--a specific angiotensin II receptor antagonist--in the prevention of hepatic fibrosis and portal hypertension. METHODS/RESULTS (1) In CCl(4) rats, losartan at 5 and 10 mg/kg per day significantly decreased portal pressure (-11, -18%, respectively), splenorenal shunt blood flow (-60, -80%) and liver fibrosis (liver hydroxyproline and area of fibrosis) without significant changes in mortality and mean arterial pressure (MAP). (2) In bile duct ligated (BDL) rats, losartan at 5 mg/kg per day significantly decreased portal pressure (-14%), splenorenal shunt blood flow (-70%) and liver fibrosis. Losartan at 10 mg/kg per day significantly worsened liver and renal functions, mortality and liver fibrosis, without significant changes in portal pressure and splenorenal shunt blood flow. Losartan at 5 and 10 mg/kg per day significantly decreased MAP (-24, -30%). (3) In portal vein ligated (PVL) rats, losartan significantly decreased MAP (-12%) but did not change portal pressure or splenorenal shunt blood flow. CONCLUSIONS In BDL and CCl(4) rats, losartan has beneficial effects on splanchnic hemodynamics and liver fibrosis. Losartan might decrease hepatic resistances in fibrotic liver. Losartan decreased MAP except in CCl(4) rats. Higher dosage of losartan had deleterious effects in BDL rats.

Prothrombin index is an indirect marker of severe liver fibrosis

Objective The non-invasive diagnosis of liver fibrosis is based mainly on biochemical markers. The main aim was to validate whether the prothrombin index is an indirect marker of the severity of liver fibrosis. Patients and methods The predictive value of the prothrombin index for liver fibrosis was first assessed in 243 patients with chronic liver disease, then validated in 193 other patients with chronic liver disease. The reproducibility of measurement of the prothrombin index in different laboratories was evaluated in 82 other patients. Results In the first group, the prothrombin index was predicted accurately by serum hyaluronate (R2 = 0.67 at the first step by multiple regression). The relationship between the prothrombin index and the area of fibrosis was not influenced significantly by non-fibrotic pathological lesions. The prothrombin index began to decrease when the Metavir fibrosis score was 2 versus 3 for albumin. In the second group, the prothrombin index and the histological fibrosis score were well correlated (r =− 0.70, P < 10–4). Prothrombin index ⩽80% or ⩽70% diagnosed severe fibrosis or cirrhosis, respectively, and prothrombin index ⩾105% or ⩾100% excluded a diagnosis of severe fibrosis or cirrhosis, respectively, at the 95% probability level. The prothrombin indices measured in different laboratories were similar (78 ± 18%v. 78 ± 14%) and well correlated (r = 0.91, P < 10–4). Conclusions The prothrombin index was well correlated with pathological liver fibrosis score, had a high diagnostic accuracy for severe fibrosis or cirrhosis especially due to alcohol, and was not influenced by other pathological lesions. The prothrombin index was reproducible. Thus, the prothrombin index expressed as a percentage is an accurate, reproducible, inexpensive and easily available marker of severe liver fibrosis.

late recurrence of a hepatic angiomyolipoma

Angiomyolipomas are benign mesenchymal tumours, mostly of renal origin. Hepatic angiomyolipomas are rare, and radiological and pathological diagnoses may be difficult We report on the first case of hepatic angiomyolipoma recurrence known to us, 6 years after surgical treatment of the initial tumour. Moreover, this hepatic recurrence was associated with renal angiomyolipoma without any stigmata of tuberous sclerosis.

Diagnosis and measurement of liver fibrosis by MRI in bile duct ligated rats

The noninvasive evaluation of liver fibrosis is a major clinical goal in liver diseases. Our aim was to identify MRI parameters to quantify liver fibrosis in vivo in an animal model of liver fibrosis with slight inflammation. We evaluated serum hyaluronate, liver hydroxyproline, area of liver fibrosis (image analysis), and 1.5-T MRI in 10 sham rats and 24 bile duct ligated rats with different stages of liver fibrosis. Liver signal intensity (SI)/muscle SI ratio and liver relaxation times (rT) were measured on T1 and T2 weighted sequences at different echo (TE) or recovery (RT) times of MRI. Among the 66 MRI parameters tested, the highest correlation with the area of fibrosis was observed for rT2 (r=0.78, P < 0.01). The area of liver fibrosis was independently predicted by five MRI variables (adjusted R2=0.78, with R2=0.64 for rT2 and rT1). Diagnostic accuracy for liver fibrosis was 100% using two variables: liver/muscle SI ratio on T2 at 30-ms TE and liver/muscle SI ratio on T1 at 50-ms RT. We conclude that in this animal model, fibrosis could be diagnosed with an accuracy of 100% using two MRI parameters. The quantification of liver fibrosis was very accurate either with only one MRI parameter (r=0.78 for rT2) or with five parameters (r=0.90) in this cholestatic model.

Hepatic hyper-vitaminosis A: importance of retinyl ester level determination.

&NA; We report the case of a 32‐year‐old man with portal hypertension without cirrhosis due to chronic vitamin A intoxication. Portal hypertension revealed by oesophageal varice rupture progressively worsened and ascites occurred 5 years after the patient stopped vitamin A intake. Initially, serum retinyl palmitate concentration was increased whereas serum retinol concentration was normal. There was no hepatic fibrosis on light microscopic examination of liver biopsy specimens. Five years after the patient stopped excessive vitamin A intake, serum retinol and retinol‐binding protein concentrations were below the normal range even though there was an increased hepatic retinyl ester content. This was attributed to the late development of peri‐sinusoidal fibrosis. This case mainly shows the importance of retinyl ester level determination: serum retinyl palmitate should be measured immediately after intoxication and hepatic retinyl esters should be measured initially and particularly later. Indeed, later serum and hepatic retinol levels in chronic hyper‐vitaminosis A may be normal and lead to under‐estimation of liver vitamin A overload. Eur J Gastroenterol Hepatol 12:361‐364

Révélation d'une tumeur stromale mésentérique par une complication de la coloscopie

Un homme de 60 ans était hospitalisé en août 2002 dans notre unité pour des douleurs abdominales associées à une hyperthermie. Il était traité depuis plusieurs années pour un diabète de type 2 correctement équilibré et n’avait pas d’autre antécédent. Deux semaines plus tôt une coloscopie de dépistage avait été réalisée sans difficulté technique permettant la résection d’un polype pédiculé de 20 mm du colon transverse. Aucune complication immédiate n’était notée et le malade était rentré à son domicile quelques heures plus tard. L’examen histologique du polype montrait un adénome tubulo-villeux. Les jours suivant la coloscopie, le malade avait présenté des douleurs abdominales et une distension abdominale d’installation progressive. Vingt-quatre heures avant l’hospitalisation, une hyperthermie à 39°5 C avec frissons était apparue. La palpation abdominale révélait une masse arrondie et tendue s’étendant de la région péri-ombilicale à la région sus-pubienne. Le toucher rectal était normal. Le bilan biologique montrait une anémie (hémoglobine : 10,7 g/dL contre 15,8 g/dL en mars 2002) normocytaire (VGM = 88) et un syndrome inflammatoire (protéine C réactive : 152 mg/L). L’échographie et le scanner abdominaux confirmaient la présence d’une volumineuse masse de 20 cm de contenu liquidien située dans le mésentère, hypodense, avec une prise de contraste au temps artériel au contact du mésentère (figure 1). Il n’était pas observé d’adénopathie. Une ponction guidée sous contrôle scannographique permettait de prélever 2,7 L de liquide sanglant et purulent. L’examen bactériologique et anatomo-pathologique de ce liquide montrait la présence de Streptococcus Anginosus sans cellules néoplasiques. Le 13 août une laparoscopie était réalisée confirmant la présence d’une volumineuse masse mésentérique avec une paroi épaisse. Son exérèse nécessitait une conversion en laparotomie avec résection cunéiforme de l’intestin grêle. L’examen anatomo-pathologique montrait une tumeur mésenchymateuse d’aspect pseudo-kystique, nécrotique et très hémorragique pesant 600 g et mesurant 16 cm dans son plus grand axe, avec une paroi de 3 cm. L’indice mitotique était modéré (score 2) et l’immuno-marquage montrait qu’il s’agissait d’une tumeur stromale CD 117+. La résection chirugicale étant considérée comme complète, aucun traitement complémentaire n’était proposé. En mars 2004, le malade était en bon état général et le scanner abdominal ne montrait pas de récidive.