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Background: In patients with cirrhosis the onset of clinically significant portal hypertension (CSPH; i.e., hepatic venous pressure gradient (HVPG) ≥ 10 mmHg) is associated with an increased risk of complications. However, most cirrhotic patients already have CSPH at presentation, and limited information is available on further risk stratification in this population. This study assessed the prognostic value of a single HVPG measurement and Doppler-ultrasound (US) evaluation in patients with cirrhosis and CSPH., Methods: Eighty-six consecutive patients with cirrhosis (73% compensated) and untreated CSPH (mean HVPG 17.8 ± 5.1 mmHg) were included. All were studied by paired HVPG and US, and followed up for a minimum of 12 months (mean 28 ± 20 months)., Results: Sixteen (25.3%) patients developed a first decompensation, and 11.6% died on follow-up. HVPG (per 1 mmHg increase OR 1.22, 95% CI 1.05-1.40, p = 0.007) and bilirubin (per 1 mg/ml increase OR 2.42, 95% CI 0.93-6.26, p = 0.06) independently predicted first decompensation, and Model for End-Stage Liver Disease (MELD) score (per 1 point increase OR 1.24, 95% CI 1.03-1.51, p = 0.03) and HVPG (per 1 mmHg increase OR 1.08, 95% CI 1.01-1.26, p = 0.05) independently predicted mortality. The best HVPG cutoff predicting these events was 16 mmHg. Ultrasonographic parameters lacked independent predictive value. The ultrasonographic detection of abdominal collaterals had a high positive likelihood ratio (7.03, 95% CI 2.23-22.16) for the prediction of HVPG ≥ 16 mmHg, implying an increase of the probability of belonging to this higher-risk population from 58 to 91%., Conclusions: HVPG holds an independent predictive value for first decompensation and death in patients with CSPH. The ultrasonographic detection of collaterals allows the non-invasive identification of patients with HVPG ≥ 16 mmHg, who are at higher risk.

Purpose: To prospectively assess if ageing itself induces modifications of the impedance indices (resistance and pulsatility indexes) of hepatic, splenic, superior mesenteric and renal arteries in patients with liver cirrhosis., Materials and Methods: 78 consecutive patients with cirrhosis (41 males, 37 females, Child-Pugh score 7 [range 5 - 12]) were studied by colour-Doppler ultrasound. The resistance index (RI) and pulsatility index (PI) were determined in the main hepatic artery, intraparenchymal branches of hepatic, splenic, and renal arteries, and superior mesenteric artery; clinical data were simultaneously collected. Logistic regression analysis was performed to assess the relative impact of age, severity of liver disease and other relevant variables on the increase of impedance indices. Linear regression analysis was used to identify a coefficient to adjust RIs and PIs to age., Results: Resistance and pulsatility indices of all the vessels studied except of the superior mesenteric artery showed a direct correlation with age (e. g. splenic artery RI: R = 0.520, p < 0.0001), and correlated most strongly with Child-Pugh score (e. g. right renal artery PI: R = 0.462, p < 0.0001). Age was associated independently with increased PI and RI in hepatic, splenic and renal arterial districts. In these vessels, the RI threshold of normality can be adjusted to the decade of age adding a correction of 0.03., Conclusion: Ageing itself induces an increase of hepatic, splenic and renal impedance indices in cirrhotic patients. The threshold of normality for these indices in cirrhosis should be adjusted according to the patients' age.

Unlabelled: Portal hypertension, the most important complication in patients with cirrhosis of the liver, is a serious and life-threatening disease for which there are few therapeutic options. Because angiogenesis is a pathological hallmark of portal hypertension, the goal of this study was to determine the effects of sorafenib-a potent inhibitor of proangiogenic vascular endothelial growth factor receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFR-beta), and Raf kinases-on splanchnic, intrahepatic, systemic, and portosystemic collateral circulations in two different experimental models of portal hypertension: rats with prehepatic portal hypertension induced by partial portal vein ligation and rats with intrahepatic portal hypertension and secondary biliary cirrhosis induced by bile duct ligation. Such a comprehensive approach is necessary for any translational research directed toward defining the efficacy and potential clinical application of new therapeutic agents. Sorafenib administered orally once a day for 2 weeks in experimental models of portal hypertension and cirrhosis effectively inhibited VEGF, PDGF, and Raf signaling pathways, and produced several protective effects by inducing an approximately 80% decrease in splanchnic neovascularization and a marked attenuation of hyperdynamic splanchnic and systemic circulations, as well as a significant 18% decrease in the extent of portosystemic collaterals. In cirrhotic rats, sorafenib treatment also resulted in a 25% reduction in portal pressure, as well as a remarkable improvement in liver damage and intrahepatic fibrosis, inflammation, and angiogenesis. Notably, beneficial effects of sorafenib against tissue damage and inflammation were also observed in splanchnic organs., Conclusion: Taking into account the limitations of translating animal study results into humans, we believe that our findings will stimulate consideration of sorafenib as an effective therapeutic agent in patients suffering from advanced portal hypertension.

Background & Aims: Splenomegaly is observed in most but not all patients with cirrhosis, and has been detected more often in patients showing complications of portal hypertension. We aimed to test the hypotheses that spleen enlarges over time in cirrhosis, and that a progressive enlargement may be associated with portal hypertension-related events., Methods: A total of 127 cirrhotic patients (Child-Pugh, 6.7 +/- 1.7; range, 5-11), observed at our center and followed-up clinically, endoscopically, and with periodic abdominal ultrasound for at least 1 year, were included. Spleen diameter was recorded at each ultrasound examination. The change of spleen diameter over time was calculated. The occurrence of clinical complications of cirrhosis on follow-up evaluation was recorded., Results: At inclusion, spleen diameter was 14.9 +/- 3.1 cm; 83% of the patients had splenomegaly. Spleen was larger in patients with decompensated disease (n = 39) versus patients with compensated disease (n = 88) (16.1 +/- 3.5 vs 14.5 +/- 2.7; P = .012). The mean follow-up period was 53 +/- 37 months. Spleen progressively enlarged over time (analysis of variance, P < .0001). A total of 46.4% of patients showed a spleen enlargement of 1 cm or more at 1 year. Over 5 years of follow-up evaluation patients showing spleen enlargement showed a higher actuarial probability of esophageal varices formation (84.6% vs 16.6%; P = .001) and growth (63.3% vs 20.6%; P = .001). Among patients with compensated cirrhosis at inclusion, those showing a spleen enlargement had a higher actuarial probability of developing the first clinical decompensation of cirrhosis (51.1% vs 19.5%, P = .002)., Conclusions: Spleen enlargement at follow-up evaluation outlines a subgroup of cirrhotic patients at higher risk of complications of portal hypertension. Noninvasive monitoring of spleen diameter allows a prognostic stratification of cirrhotic patients.