Rifflet H

Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis

BACKGROUND/AIMS Evaluation of the degree of hepatic fibrosis is especially important in patients with chronic liver disease. Our aim was to study the diagnostic accuracy of abdominal ultrasonography for cirrhosis or fibrosis. METHODS Twenty-three clinical (n=12) and Doppler ultrasonic (n=11) variables were recorded in 243 patients with chronic (alcoholic and viral) liver disease under conditions close to those of clinical practice. Fibrosis was classified into six grades by two pathologists. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables, then by stepwise analysis. RESULTS A) Diagnosis of cirrhosis: 1) whole group (n=243): diagnostic accuracy was globally 84%, and 84% with two variables: spleen length, portal velocity; 2) compensated chronic liver disease (n=191): diagnostic accuracy was globally 85%, and 82% with two variables: liver surface, liver length (right kidney); 3) alcoholic compensated chronic liver disease (n=109): diagnostic accuracy was globally 86%, and 88% with two variables: spleen length, liver length (middle clavicle); 4) viral compensated chronic liver disease (n= 83): diagnostic accuracy was globally 86% and 86% with one variable: liver surface. By subtracting the proportion of patients who could not be investigated due to anatomical limitations, the highest calculated univariate diagnostic accuracy decreased by 7%. B) Diagnosis of fibrosis: diagnostic accuracy was globally 84% for extensive fibrosis. CONCLUSIONS Cirrhosis can be correctly diagnosed in 82-88% of patients with chronic liver disease using a few ultrasonographic signs. However, the diagnostic accuracy of ultrasound is decreased by the anatomical limitations of this technique.

Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores: Comparison with serum markers

BACKGROUND/AIMS Liver fibrosis is mainly evaluated by qualitative histological examination. Although histological semi-quantitative scores and quantitative determination with image analysis are now possible, these methods have not been fully validated and compared. Therefore, we evaluated these two methods prospectively in 243 patients with chronic liver disease. METHODS The semi-quantitative fibrosis score was evaluated by two independent pathologists, using the Knodell fibrosis score and a 6-grade score derived from the Metavir score; the area of fibrosis was measured by image analysis. The serum levels of hyaluronate, N-terminal peptide of procollagen III, laminin, transforming growth factor-beta1, alpha2-macroglobulin, apolipoprotein A1, PGA score and prothrombin index were measured. RESULTS There was a good correlation between the semi-quantitative fibrosis score and the area of fibrosis (r=0.84, p<10(-4)). Using multiple regression analysis, the semi-quantitative score was predicted by the 8 serum markers with R2=0.69 (R2=0.59 for hyaluronate at the 1st step) while the area of fibrosis was predicted with R2=0.79 (R2=0.76 for hyaluronate at the 1st step), and the Knodell fibrosis score was predicted with R2=0.65 (R2=0.31 for hyaluronate at the 1st step). CONCLUSIONS The area of fibrosis, as determined by image analysis, and the semi-quantitative score are well correlated. However, for serum markers the correlation is higher with the area of fibrosis than with the semi-quantitative score. Other characteristics such as reproducibility, rapidity, simplicity, adaptability, and exhaustiveness also favor image analysis.

Non-invasive diagnosis of esophageal varices in chronic liver diseases

BACKGROUND/AIMS The primary prevention of bleeding from esophageal varices is a major therapeutic issue requiring early screening of esophageal varices. Our aim was to study the diagnostic accuracy of non-endoscopic means for the diagnosis of esophageal varices. METHODS Sixty-three clinical, biochemical, endoscopic and Doppler ultrasound variables were prospectively recorded in 207 consecutive patients with chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables with diagnostic accuracy > or = 65% in univariate analysis, then by stepwise regression. RESULTS A) whole group (n=207), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 81%, and 81% with 1 variable: irregular liver surface at ultrasound, 2) Diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 80%, and 79% with 2 variables: prothrombin index, gamma-globulins. B) patients with cirrhosis (n=116), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 71%, and 72% with 2 variables: platelet count, prothrombin index, 2) diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 71%, and 72% with 3 variables: platelet count, prothrombin index, spider naevi. The ROC curve showed that the best threshold for the diagnostic accuracy of platelet count was 160 G/l providing a sensitivity of 80% and a specificity of 58%. Platelet count > or = 260 G/l has a negative predictive value > or = 91%. CONCLUSIONS Using a few non-endoscopic criteria, esophageal varices can be correctly diagnosed in 81% of patients with chronic liver disease and in 71% of patients with cirrhosis. These results show that the non-invasive screening of patients who are candidates for the primary prevention of variceal bleeding is possible, but should be improved before being used in a clinical setting.

Possible Zoonotic Transmission of Hepatitis E from Pet Pig to Its Owner

Hepatitis E is transmitted mainly by water or food, but in industrialized countries, all routes of transmission have not been identified. We describe possible zoonotic transmission of hepatitis E virus that involved direct contact between a pet pig and its owner.

Effects of simvastatin, pentoxifylline and spironolactone on hepatic fibrosis and portal hypertension in rats with bile duct ligation

AIMS/METHODS Our aim was to study the antifibrotic and hemodynamic effects of simvastatin (SMV), pentoxifylline (PTX) and spironolactone (SPN), three drugs which may have antifibrotic and/or portal hypotensive properties, in a model of hepatic fibrosis and portal hypertension induced in rats by bile duct ligation. A blind study was performed in five groups of 53 Sprague-Dawley rats: sham, placebo (PL), SMV (2.5 mg x kg(-1) x J(-1)), PTX (50 mg x kg(-1) x J(-1)) and SPN (100 mg x kg(-1) x J(-1)). Drugs were administered by daily gavage over a 4-week period as soon as bile duct ligation was performed. At day 28, the following parameters were evaluated: area of hepatic fibrosis by image analysis after staining collagen with picrosirius and plasma concentrations of hyaluronate, splanchnic and systemic hemodynamics (radiolabeled microspheres). RESULTS Portal venous pressure (PL: 15.5+/-1.5, SMV: 15.8+/-2.5, PTX: 15.9+/-1.8, SPN: 13.5+/-2.1 mmHg, p<0.05) and porto-systemic shunts (PL: 30+/-31, SMV: 18+/-27, PTX: 25+/-24, SPN: 5+/-4%, p<0.05) were significantly reduced in the SPN group; other hemodynamic parameters were not significantly altered. There was a significant correlation between portosystemic shunts and portal pressure (r(s)=0.47, p<0.01). The area of fibrosis was not significantly different among the four groups of bile duct ligated rats (PL: 8.7+/-3.9, SMV: 7.1+/-3.6, PTX: 7.8+/-2.7, SPN: 6.6+/-3.3%) but was higher than in sham rats (1.5+/-0.5%, p<0.001). Hyaluronate was significantly higher in bile duct ligated rats (from 374+/-162 to 420+/-131 microg/l, among the four groups) than in sham rats (52+/-16 microg/l, p<0.0001). CONCLUSIONS In this model, none of the drugs prevented hepatic fibrosis. On the other hand, spironolactone decreased portal pressure and prevented porto-systemic shunts. Therefore, this drug may have beneficial effects in patients with early portal hypertension.

Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen.

BACKGROUND/AIMS To evaluate the efficacy of ribavirin, given in second intention in non-responders to interferon alone, by studying viral kinetics. METHODS We conducted a trial including 203 patients with chronic hepatitis C, naïve of treatment. Patients were treated with interferon three times a week with or without ribavirin and amantadine according to response. Viral kinetics were assessed by serial measurements of HCV RNA (bDNA 3.0 and Monitor 2.0) and a new assay, trak-C, able to quantify total Hepatitis C virus (HCV) core antigen. RESULTS A significant initial drop in HCV RNA or HCV core antigen, under interferon alone, was associated with response to therapy, -4.85+/-1.33 log for HCV RNA in sustained responders versus -1.86+/-1.53 log for others groups, P<0.001. In patients receiving ribavirin in second intention, we also observed a similar drop in HCV RNA and HCV core antigen, predictive of sustained response, -2.67+/-1.26 log for HCV RNA in sustained responders versus -0.44+/-0.49 log in non-responders, P<0.001. CONCLUSIONS Ribavirin has probably an additional antiviral effect in interferon treated patients. Kinetics of HCV RNA and HCV core antigen under treatment are highly predictive of a sustained virological response.

Prevention of portal hypertension by propanolol and spironolactone in rats with bile duct ligation

BACKGROUND/AIMS It has been suggested that the early administration of propranolol (PR) and a low sodium diet may prevent the development of portosystemic shunts in animals with presinusoidal portal hypertension. Our aim was to study the hemodynamic effects of the early and chronic administration of PR and spironolactone (SPN), alone or in combination, in a model of hepatic fibrosis and sinusoidal portal hypertension induced in rats by bile duct ligation. METHODS A blind study was performed in 40 Sprague-Dawley rats divided into four groups: placebo (PL), PR (75 mg/kg per day), SPN (100 mg/kg per day), and PR+SPN at the same doses. Drugs were administered by daily gavage over a 4-week period as soon as bile duct ligation was performed. At day 28, the splanchnic and systemic hemodynamics (radiolabeled microspheres) were evaluated. RESULTS a) Systemic hemodynamics: PR significantly reduced cardiac index and increased vascular resistance, SPN had no significant effect and PR+SPN significantly decreased mean arterial pressure. b) Splanchnic hemodynamics: portal venous pressure (PL: 15.5 +/- 1.5, PR: 14.8 +/- 1.0, SPN: 13.5 +/- 2.1, PR+SPN: 15.0 +/- 1.3 mmHg, p < 0.05) and portosystemic shunts (PL: 30 +/- 31, PR: 13 +/- 14, SPN: 5 +/- 4, PR+SPN: 29 +/- 33%, p < 0.05) were significantly reduced in the SPN group; other hemodynamic parameters were not significantly altered. In multivariate analysis, the only determinant of portosystemic shunts was portal pressure but with a low R2 (0.2). CONCLUSIONS In this model, the early administration of PR, alone or in combination with SPN, had no beneficial hemodynamic effects. On the other hand, SPN alone decreased portal pressure and prevented portosystemic shunts. Therefore, this drug may have beneficial effects in patients with early portal hypertension.

Hemodynamic effects of terlipressin and octreotide administration alone or in combination in portal hypertensive rats

BACKGROUND/AIMS The action sites and kinetic effects of octreotide and terlipressin may be different. Therefore, we studied the hemodynamic effects of acute administration of these drugs alone or in combination in rats with portal hypertension due to portal vein ligation. METHODS In a first study performed in anesthetized rats, hemodynamics were measured before and after drug administration (placebo, octreotide: 8 microg x kg(-1) x h(-1) for 30 min, terlipressin: 50 microg/kg bolus, terlipressin + octreotide at the same doses). The second study, performed in conscious rats, included the same groups and drug doses; hemodynamics were measured every 10 min for 1 h. The third study tested the effect of preinfusion of octreotide on responsiveness to terlipressin. RESULTS Terlipressin produced more marked systemic effects than octreotide by decreasing heart rate and cardiac output and increasing mean arterial pressure. Terlipressin produced a greater decrease in portal pressure than octreotide: placebo: -3+/-5%, terlipressin: -42+/-8%, octreotide: -16+/-10%, combination: -44+/-8% (conscious rats at 20 min, p<10(-4)). The decrease in portal pressure was immediate and lasted at least 60 min with both drugs. Octreotide significantly decreased spleno-renal shunt blood flow (% variation): placebo: -6+/-8, terlipressin: -15.5+/-20, octreotide: -22.5+/-20, combination: -27+/-10 (p<10(-2)). Octreotide preinfusion significantly increased the responsiveness of arterial pressure and heart rate to terlipressin. CONCLUSIONS Terlipressin decreases portal pressure significantly more than octreotide, while only octreotide significantly decreases collateral blood flow. Simultaneous administration of these drugs does not have significant additive effects but has complementary effects. The preadministration of octreotide alters systemic response to terlipressin.