During the last decade great advances have been made of water retention and dilutional hyponatremia in human cirrhosis. Finally, the field of spontaneous infection of concerning the pathogenesis and treatment of ascites. A new hypothesis on the mechanism of renal dysfunction ascitic fluid (spontaneous bacterial peritonitis) is also experiencing major changes. The demonstration of intestiand ascites formation in cirrhosis has been proposed 1 and this has greatly stimulated research in this area. The nal bacterial translocation in experimental models of cirrhosis, 12 the potential role of cytokines in some discovery of the important role played by the vascular endothelium in the homeostasis of systemic hemodynam-complications associated with this infection, 13 the identification of subgroups of cirrhotic patients predisposed to ics and renal function 2,3 has also opened an important field of research into pathophysiology, and evidence has develop spontaneous bacterial peritonitis, 14 and the effectiveness of selective intestinal decontamination in the been presented implicating endothelial factors in the pathogenesis of systemic circulatory dysfunction in cir-primary and secondary prophylaxis of spontaneous bacterial peritonitis 15,16 are the most relevant developments. rhosis 4,5 and hepatorenal syndrome (HRS). 6 The reintroduction of therapeutic paracentesis has greatly modifiedIn clear contrast to these advances, little attention has been paid to the standardization of the nomenclathe treatment of cirrhotic patients with tense or refractory ascites. 7 The transjugular intrahepatic portosys-ture and diagnostic criteria of different syndromes associated with ascites in cirrhosis. The existence of a temic shunt is another therapeutic tool of potential interest in the management of refractory ascites. 8 The uniform language, however, is essential in modern medicine. It facilitates communication among clinisynthesis of orally-active specific antagonists of the tubular effect of antidiuretic hormone and inhibitors of antidi-cians and researchers and ensures unambiguous diagnoses and more confident prognoses. Moreover, it uretic hormone release will probably add new drugs to the pharmacological armamentarium for patients with improves pathophysiological and therapeutic investigations, simplifies the analysis of therapeutic trials, cirrhosis and ascites. These ''aquaretic drugs,'' which normalize renal water metabolism in experimental cirrhosis and stimulates multicenter studies. and ascites, 9-11 are of potential interest for the treatment PREVIOUS CONSENSUS DEFINITIONS OF HEPATORENAL SYNDROME AND

Measurement of hepatic venous pressure gradient (HVPG) is a standard method for the assessment of portal pressure and correlates with the occurrence of its complications. Liver stiffness measurement (LSM) has been proposed as a noninvasive technique for the prediction of the complications of cirrhosis. In this study, we evaluated the ability of LSM to predict severe portal hypertension compared with that of HVPG in 61 consecutive patients with HCV-related chronic liver disease. A strong relationship between LSM and HVPG measurements was found in the overall population (r ‫؍‬ 0.81, P < 0.0001). However, although the correlation was excellent for HVPG values less than 10 or 12 mm Hg (r ‫؍‬ 0.81, P ‫؍‬ 0.0003 and r ‫؍‬ 0.91, P < 0.0001, respectively), linear regression analysis was not optimal for HVPG values >10 mm Hg (r 2 ‫؍‬ 0.35, P < 0.0001) or >12 mm Hg (r 2 ‫؍‬ 0.17, P ‫؍‬ 0.02). The AUROC for the prediction of HVPG >10 and >12 mm Hg were 0.99 and 0.92, respectively and at LSM cutoff values of 13.6 kPa and 17.6 kPa, sensitivity was 97% and 94%, respectively. In patients with cirrhosis, LSM positively correlated with the presence of esophageal varices (P ‫؍‬ 0.002), although no correlation between LSM and esophageal varices size was detected. The area under the ROC for the prediction of EV was 0.76 and at a LSM cutoff value of 17.6 kPa sensitivity was 90%. Conclusion: LSM represents a non-invasive tool for the identification of chronic liver disease patients with clinically significant or severe portal hypertension and could be employed for screening patients to be subjected to standard investigations including upper GI endoscopy and hemodynamic studies.

Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels <2؋ the upper limit of normal. In all patients, the degree of liver stiffness at the time of the peak increase in aminotransferases exceeded the cutoff values proposed for the prediction of significant fibrosis or cirrhosis. A progressive significant reduction in liver stiffness values was observed (P < 0.0001) in the follow-up period in parallel with the reduction of aminotransferase levels (P < 0.0001). Moreover, a statistically significant, positive correlation between aminotransferases and liver stiffness measurement (LSM) at the onset of acute viral hepatitis was found (r ‫؍‬ 0.53, P ‫؍‬ 0.02 and r ‫؍‬ 0.51, P ‫؍‬ 0.03 for alanine aminotransferase and aspartate aminotransferase, respectively). In conclusion, the extent of necroinflammatory activity needs to be carefully considered in future studies aimed at further validating transient elastography, particularly in patients with absent or low-stage liver fibrosis (in other words, F0-F2 METAVIR). LSM does not represent a reliable instrument to detect the presence of advanced fibrosis and cirrhosis in patients presenting with a clinical picture of acute hepatitis. (HEPATOLOGY 2008;47:380-384.)

Italian Medicine Agency.

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Background: Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in patients with chronic liver disease. Aim: To assess the value of TE for predicting the stage of fibrosis. Methods: Liver biopsy and TE were performed in 150 consecutive patients with chronic hepatitis C-related hepatitis (92 men and 58 women, age 50.6 (SD 12.5) years on the same day. Necro-inflammatory activity and the degree of steatosis at biopsy were also evaluated.

Following liver injury, hepatic stellate cells (HSC) undergo proliferation and migrate into damaged areas in response to chemotactic factors. HSC have been shown to regulate leukocyte trafficking by secreting monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes and lymphocytes. In this study, we explored whether MCP-1 exerts biological actions on HSC. HSC were isolated from normal human livers, cultured on plastic, and studied in their myofibroblast-like phenotype, and three different cells lines were used. Chemotaxis was measured in modified Boyden chambers. The tissue response to injury involves the coordinated recruitment and activation of a number of cells in the attempt to repair the damage provoked by toxic, infectious, or immunological mechanisms. Inflammatory cells recruited at sites of damage are responsible for the scavenging of the necrotic cells, whereas myofibroblasts secrete extracellular matrix components and restore the integrity of the tissue. Within the liver, hepatic stellate cells (HSC) are responsible for this second part of the wound-healing response. 1,2 In normal liver, HSC fulfill the role of retinoid storage and metabolism, and their phenotype is referred to as quiescent. However, following injury, HSC undergo differentiation toward an activated phenotype characterized by proliferation and increased secretion of extracellular matrix components. This process is associated with enhanced or de novo expression of receptors for several soluble mediators, such as platelet-derived growth factor (PDGF), transforming growth factor-␤, or thrombin, which mediate the increase in cell proliferation and extracellular matrix production. [3][4][5] Therefore, HSC are the main cell type involved in the deposition of matrix that leads to fibrosis and cirrhosis. Another feature of cells involved in tissue repair is their ability to migrate into the damaged areas according to concentration gradients of chemotactic factors. 6 We have recently shown that HSC share this ability to respond to chemotactic factors such as PDGF. 7 Recent investigation has pointed out additional characteristics of the HSC that are relevant for the hepatic wound healing response. 2 HSC have been shown to express several molecules that are capable of regulating leukocyte trafficking, including chemokines. [8][9][10][11][12] These latter are a group of cytokines that exhibit chemoattractant properties for relatively specific groups of leukocytes. Four classes of chemokines have been recognized according to the position of conserved cysteine residues and differences in the spectrum of target cells. 13 The group of CXC chemokines includes a variety of factors, such as interleukin-8, which are mainly, but not exclusively, chemotactic for neutrophils. 13 Lymphotactin, a cytokine that specifically attracts lymphocytes, is the only known member of the C class of chemokines. 13 A novel cell-associated chemokine characterized by a CX3C motif and higher molecular weight has been recently identified. 14 Chemokines of the ...