Fabienne Pessione

Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria.

BACKGROUND & AIMS The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC). METHODS Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic score was developed and validated in a national cohort of 435 patients followed up prospectively. RESULTS α-Fetoprotein (AFP) independently predicted tumor recurrence and correlated with vascular invasion and differentiation. At a Cox score threshold of 0.7 (area under the receiver operating characteristic curve, 0.701; 95% confidence interval, 0.63-0.76; accuracy, 75.8%), a model combining log(10) AFP, tumor size, and number was highly predictive of tumor recurrence and death. By using a simplified version of the model, with untransformed AFP values, a cut-off value of 2 was identified. In the validation cohort, a score greater than 2 predicted a marked increase in 5-year risk of recurrence (50.6% ± 10.2% vs 8.8% ± 1.7%; P < .001) and decreased survival (47.5% ± 8.1% vs 67.8% ± 3.4%; P = .002) as compared with others. Among patients exceeding Milan criteria, a score of 2 or lower identified a subgroup of patients with AFP levels less than 100 ng/mL with a low 5-year risk of recurrence (14.4% ± 5.3% vs 47.6% ± 11.1%; P = .006). Among patients within Milan criteria, a score greater than 2 identified a subgroup of patients with AFP levels greater than 1000 ng/mL at high risk of recurrence (37.1% ± 8.9% vs 13.3% ± 2.0%; P < .001). Net reclassification improvement showed that predictability of the AFP model was superior to Milan criteria. CONCLUSIONS Prediction of tumor recurrence is improved significantly by a model that incorporates AFP. We propose the adoption of new selection criteria for HCC transplant candidates, taking into account AFP.

Five‐year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence

Abstract:  Aim: To evaluate 5‐year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow‐up.

Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with Terlipressin: A retrospective analysis

Abstract Background and Aim: Terlipressin has been proposed to treat renal failure in patients with type 1 hepatorenal syndrome (HRS). However, the predictive factors for improved renal function and survival are unknown in patients with type 1 HRS treated with terlipressin. The aim of the present retrospective study was to investigate the predictive factors and prognosis of patients with type 1 HRS treated with terlipressin.

Coagulation disorders in patients with cirrhosis and severe sepsis

Background: In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation.

Clinical characteristics and outcome of patients with cirrhosis and refractory ascites.

Abstract: Background: In patients with cirrhosis, refractory ascites is associated with a poor prognosis and is an indication for liver transplantation. However, factors that determine prognosis remain unclear.

Aquaretic effects of niravoline, a κ-opioid agonist, in patients with cirrhosis

Abstract Background/Aims : In patients with cirrhosis, decreased renal water excretion is a common complication. Niravoline (RU51599), a κ -opioid receptor agonist, has been shown to induce an aquaretic response. The aim of this study was to evaluate the aquaretic effect and tolerance of niravoline in patients with cirrhosis. Methods : Biochemical tests and hemodynamic values were determined before and 1, 2, 3 and 24 h after niravoline administration at doses ranging from 0.5 to 2 mg iv in 18 patients with cirrhosis. Results : Diuresis significantly increased in the first hour from 64±9 to 146±31 ml/h, and returned to basal values after 3 h. Free water clearance also significantly increased, reaching the positive range at 1 h. Plasma osmolality significantly decreased at 2 h (from 290±4 to 286±4 mOsm/kg). Plasma sodium concentrations increased significantly at 3 h (from 133±1 to 134±1 mEq/l). Heart rate and arterial pressure did not change. The highest doses (1.5 mg or 2 mg) induced personality disorders and mild confusion within 2 h. These effects reversed completely within 8 h. Conclusion : This study shows that niravoline administration induces an aquaretic response and is well tolerated, at moderate doses, in patients with cirrhosis. Thus, moderate doses of niravoline may be useful for treating patients with cirrhosis and water retention.

Role of small-conductance Ca2+-dependent K+ channels in in vitro nitric oxide-mediated aortic hyporeactivity to α-adrenergic vasoconstriction in rats with cirrhosis

BACKGROUND/AIMS In vitro studies have shown that cirrhotic aortas are hyporeactive to the contractile effect of vasoconstrictors because upregulated endothelial nitric oxide-synthase (NOS) overproduces nitric oxide (NO). Although stimulation of endothelial small-conductance Ca2+-dependent K+ (SK(Ca)) channels may elicit vasorelaxation in normal arteries, the role of these channels in cirrhosis-induced hyporeactivity is unknown. Thus, the aim of the present study was to investigate the role of endothelial SK(Ca) channels in cirrhosis-induced, NO-mediated, in vitro aortic hyporeactivity to alpha1-adrenergic vasoconstrictors. METHODS Isolated thoracic aortas from cirrhotic and normal rats were used. The effects of apamin, a selective SK(Ca) channel blocker, were measured on the vascular reactivity to phenylephrine. In addition, SK(Ca) channel protein expression was studied. The effects of iberiotoxin and charybdotoxin, blockers of other K(Ca) channels, were also studied in cirrhotic aortas. RESULTS Apamin suppressed cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent, NOS-inhibitor-sensitive manner. SK(Ca) channel protein was overexpressed in cirrhotic aortic walls. Iberiotoxin abolished cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent but NOS-inhibitor-resistant manner. Charybdotoxin did not induce any significant increase in phenylephrine-elicited contraction. CONCLUSIONS In cirrhotic aortas, the overexpression and overactivity of endothelial SK(Ca) channels contributes to in vitro NO-mediated hyporeactivity to the contractile action of alpha1-adrenergic agonists.

Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis

Objective In patients with cirrhosis, the relationships between haemodynamic alterations and the development of ascites or the occurrence of refractory ascites are unknown. The aim of the present study was to compare haemodynamic measurements obtained in patients with non-refractory ascites to haemodynamic measurements obtained in patients without ascites and in patients with refractory ascites. Methods A cohort of 121 patients was prospectively studied, of whom 29 patients did not have ascites, 45 had non-refractory ascites and 47 had refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in all patients. Results The hepatic venous pressure gradient was significantly higher in patients with non-refractory ascites than in patients without ascites (18.5 ± 0.8 mmHg versus 15.8 ± 0.7 mmHg). Renal and systemic haemodynamics did not significantly differ between patients with non-refractory ascites and patients without ascites. The glomerular filtration rate and renal blood flow were significantly lower in patients with refractory ascites than in patients with non-refractory ascites (77 ± 4 versus 107 ± 5 ml/min and 867 ± 62 versus 1008 ± 68 ml/min, respectively). Splanchnic and systemic haemodynamics did not significantly differ between patients with refractory ascites and patients with non-refractory ascites. Conclusions In patients with cirrhosis, an increase in portal hypertension was the sole haemodynamic alteration related to the development of ascites. Renal vasoconstriction (and subsequent renal hypoperfusion and hypofiltration) was the only haemodynamic alteration related to the occurrence of refractory ascites. The development of ascites or refractory ascites was not associated with any alteration in systemic haemodynamics.