Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis

Portal hypertension is a clinical syndrome which leads to several clinical complications,such as the formation and rupture of esophageal and/or gastric varices,ascites,hepatic encephalopathy and hepato-renal syndrome.In cirrhosis,the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow.However,also an increase in splanchnic blood flow worsens and maintains portal hypertension.The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow.Several vasoactive systems/substances,such as nitric oxide,cyclooxygenase-derivatives,carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation.Moreover,an impaired reactivity to vasoconstrictor systems,such as the sympathetic nervous system,vasopressin,angiotensinⅡand endothelin-1,plays a role in this process.The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels,but also through the generation of new vessels.Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome,a syndrome which occurs in pa-tients with portal hypertension and is characterized by increased cardiac output and heart rate,and decreased systemic vascular resistance with low arterial blood pressure.Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.

Covert hepatic encephalopathy: Agreement and predictive validity of different indices

AIM:To investigate the agreement and prognosticvalue of different measures of covert hepatic encephalopathy(CHE).METHODS:One-hundred-and-thirty-two cirrhotic outpatients underwent electroencephalography(EEG),paper-and-pencil psychometry(PHES)and critical flicker frequency,scored on the original/modified(CFFo/CFFm)thresholds.Eighty-four patients underwent Dopplerultrasound to diagnose/exclude portal-systemic shunt.Seventy-nine were followed-up for 11±7 mo in relation to the occurrence of hepatic encephalopathy(HE)-related hospitalisations.RESULTS:On the day of study,36%had gradeⅠHE,42%abnormal EEG,33%abnormal PHES and 31/21%abnormal CFFo/CFFm.Significant associations were observed between combinations of test abnormalities;however,agreement was poor(Cohen’sκ<0.4).The prevalence of EEG,PHES and CFFo/CFFm abnormalities was significantly higher in patients with gradeⅠovert HE.The prevalence of EEG and CFFm abnormalities was higher in patients with shunt.The prevalence of EEG abnormalities was significantly higher in patients with a history of HE.During follow-up,10 patients died,10were transplanted and 29 had HE-related hospitalisations.GradeⅠHE(P=0.004),abnormal EEG(P=0.008)and abnormal PHES(P=0.04)at baseline all predicted the subsequent occurrence of HE;CFF did not.CONCLUSION:CHE diagnosis probably requires a combination of clinical,neurophysiological and neuropsychological indices.

Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in patients with cirrhosis and small varices

AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 1[24.09%(95%CI:14.89%-33.29%)]was significantly lower than in Strategy 2[60.00%(95%CI:48.91%-71.08%)].The mean cost(up to the first event)associated with Strategy 1[823￡(95%CI:106￡-2036￡)]was not significantly different from that of Strategy 2[799￡(95%CI:0￡-3498￡)].The cost-effectiveness ratio with respect to this endpoint was equal to 50.26￡(95%CI:-504.37￡-604.89￡)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028￡(95%CI:122￡-2581￡),while 1699￡(95%CI:171￡-4674￡)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.