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Abstract: We describe an interesting case of a woman with decompensated cirrhosis, ischaemic heart disease and prolonged QT interval, who developed a new-onset atrial fibrillation. During amiodarone infusion a torsade de pointes occurred, which was immediately converted to sinus rhythm by synchronized cardioversion. A new episode of atrial fibrillation was treated with infusion of a beta-blocker (metoprolol) that restored sinus rhythm and normalized the QT interval. Delayed repolarization, frequently observed in ischaemic heart disease, cirrhosis and pro-arrhythmic drugs administration, represents the background for the development of torsade de pointes. Our report underlines that the potential harmfulness of a prolonged QT interval in cirrhotic patients is currently not perceived in its entirety, so that various categories of drugs affecting ventricular repolarization are rather thoughtlessly used in clinical practice without monitoring the QT interval. Thus, amiodarone should be avoided, if possible, or used with extreme care in arrhythmic patients with advanced liver disease. Moreover, beta-blockers may be considered the first-line treatment for rate-control during supraventricular tachyarrhythmias in cirrhotic patients with delayed repolarization. [Copyright &y& Elsevier]

Background & Aims: Endocannabinoids contribute to hemodynamic abnormalities of cirrhosis. Whether this favors renal sodium retention and ascites formation is unknown. We determined whether cannabinoid type 1 receptor antagonism prevents sodium retention and ascites formation in preascitic cirrhotic rats. Methods: Once renal sodium handling was impaired, rats with carbon tetrachloride–induced cirrhosis were randomized to receive either vehicle or rimonabant (3 [group 1] or 10 [group 2] mg·kg−1 ·day−1) for 2 weeks. Natriuresis, sodium intake, and sodium balance were measured daily. At the end of the protocol, systemic hemodynamics, renal blood flow, ascites volume, and liver fibrosis were assessed. Results: A significant reduction in ascites formation (group 1: 54%; group 2: 10%; vehicle: 90%) and volume (group 1: 1.6 ± 0.3 mL; group 2: 0.5 mL; vehicle: 5.5 ± 0.8 mL) occurred in treated rats. Rimonabant significantly improved sodium balance during week 2 (group 1: 0.98 ± 0.08 mmol; group 2: 0.7 ± 0.08 mmol; vehicle: 3.05 ± 0.11 mmol). Both treated groups showed lower cardiac output and higher mean arterial pressure, peripheral vascular resistance, and renal blood flow (P < .05). Liver fibrosis was reduced in group 2 by 30% (P < .05 vs vehicle). Mean arterial pressure inversely correlated with sodium balance (R = −0.61; P = .003), but not with fibrosis score. Conclusions: Rimonabant improves sodium balance and delays decompensation in preascitic cirrhosis. This is achieved though an improvement in systemic and renal hemodynamics, although it cannot be excluded that the antifibrotic effect of the drug may play a role. [Copyright &y& Elsevier]

Abstract: Background.: Thalidomide, an anti-angiogenic agent, does not have a good therapeutic effect for advanced hepatocellular carcinoma when used alone. Megestrol and interleukin-2 have been proposed as a palliative treatment for hepatocellular carcinoma. Aims.: We assessed the effectiveness/safety of a combined therapy with thalidomide+megestrol+interleukin-2 in cirrhotic patients with advanced hepatocellular carcinoma. Patients and methods.: Nine cirrhotic patients with advanced hepatocellular carcinoma received oral megestrol (160mg/day) and thalidomide (from 50mg/day to the maximal tolerated dose). Four patients also received subcutaneous interleukin-2 (1 million U/day for 21 days/month). Results.: The maximal tolerated dose of thalidomide was 150mg/day. All patients complained of sedation and other neurological or digestive adverse effects. In all but one patient the adverse effects disappeared after thalidomide withdrawal or dose reduction. Interleukin-2 administration caused a flu-like syndrome and a reaction at the injection site. During treatment, alpha-fetoprotein increased in six patients, remained stable in two and decreased in one. Eight patients showed tumour progression and one had a stable disease. Eight patients died. The median survival was 9.9 (range 2.6–18.6) months. Conclusion.: In cirrhotic patients, the combined treatment with thalidomide+megestrol (±interleukin-2) does not control hepatocellular carcinoma growth, possibly due to the low tolerance to thalidomide and interleukin-2 preventing the use of appropriate dosages. [Copyright &y& Elsevier]

Abstract: We report a case of a 65-year-old woman with hepatitis C virus-related decompensated cirrhosis with hepatorenal syndrome, treated by high dose of terlipressin. Few hours after the highest dose was started, the patient complained burning pain in breasts, followed by the development of extensive bilateral cyanosis of breast''s skin. When terlipressin was immediately stopped, pain and skin cyanosis rapidly disappeared. The peculiarity of our case is that cyanosis did not develop in common peripheral sites (e.g. fingers, toes, etc.) but in an atypical area, as skin of the breasts. Probably, this particular behaviour could be explained by the anatomical position of her large size breasts, that resulting as an extremely sloping and stretching region thus filling the maximum effect of gravity. [Copyright &y& Elsevier]