Treatment of hepatorenal syndromes (HRSs) is currently based on vasopressin analogs. The aim of this pilot study was to evaluate the efficacy and safety of noradrenalin (NA) in the treatment of type 1 HRS. Between 1998 and 2000, 12 consecutive patients with type 1 HRS (7 men, 5 women; mean age, 54 ؎ 11 years; mean Child-Pugh score, 11.3 ؎ 1.7) were treated with intravenous NA (0.5-3 mg/h), in combination with intravenous albumin and furosemide. NA was given for 10 ؎ 3 days, at a mean dose of 0.8 ؎ 0.3 mg/h. Reversal of HRS was observed in 10 of 12 patients (83%; 95% confidence interval, 52%-98%) after a median of 7 days (range, 5-10 days). Serum creatinine levels fell from 358 ؎ 161 to 145 ؎ 78 mol/L (P < .001), creatinine clearance rose from 13 ؎ 9 to 40 ؎ 15 mL/min (P ‫؍‬ . H epatorenal syndrome (HRS) is a frequent and major complication of end-stage cirrhosis. It is considered as a functional renal failure caused by marked renal vasoconstriction, related to peripheral (mainly splanchnic) arterial vasodilation. 1 Type 1 HRS usually occurs in patients with end-stage liver disease and shows a poor prognosis. The median survival time is about 10 days. It is defined as rapidly progressive renal failure with a 50% reduction in initial creatinine clearance to below 20 mL/min within 15 days. 2 Type 2 HRS occurs instead in patients with refractory ascites and is characterized by moderate and more stable impairment of renal function. Liver transplantation is the only treatment to improve survival in patients with type I HRS 3 ; however, because of the very poor prognosis of type 1 HRS and because of organ shortage, a donor is usually not found quickly enough to avoid death. HRS management thus focuses on improving renal function and thereby extending survival pending liver transplantation. This has recently been addressed by assessing the effects of vasoconstrictors that, combined with plasma expanders, restore the collapse of systemic vascular resistances (SVRs) underlying HRS. 1,4-9 Thus, vasopressin analogs such as ornipressin 4-6 and terlipressin 7-9 improve renal perfusion and glomerular filtration in patients with HRS by inducing vasoconstriction of the splanchnic circulation.Noradrenalin (NA) is a catecholamine with predominantly ␣-adrenergic activity. Given its vasoconstricting effects in venous and arterial systems, and its limited action on the myocardium, it is currently the drug of choice for vasoplegic shock. These pharmacologic properties suggest that NA might also counteract the collapse in SVRs leading to HRS. After a case report of successful treatment of HRS with a combination of NA and dopamine, 10 we conducted a pilot study to Abbreviations: HRS, hepatorenal syndrome; SVR, systemic vascular resistance; NA, noradrenalin; CVP, central venous pressure; MAP, mean arterial pressure. From the

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We believe that optimal management of these patients with chronic spontaneous encephalopathy is liver transplantation.

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Summary Background The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated. Aims To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants. Methods A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non‐endoscopic treatment (surgery or interventional radiology). Results Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index ≥ 5 and UGIB occurrring in in‐patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non‐endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant. Conclusion DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.

We report the case of a 45-year-old man with HCV treated with pegylated interferon-alpha/ribavirin, in whom fatal cardiomyopathy occurred. Cardiomyopathy is a rare complication of high dose of standard interferon but has never been reported with pegylated interferon. The relationship between pegylated interferon-alpha/ribavirin and the development of cardiomyopathy is highly probable for the following reasons: (1) a cardiologist consultation with specific investigations had been performed before treatment excluding a pre-existing cardiomyopathy; (2) symptoms of advanced dilated cardiomyopathy appeared immediately after the end of treatment; (3) other causes of cardiomyopathy have been ruled out. In all except one of the 21 reported cases with standard interferon, cardiomyopathy was reversible. In our patient, fatal cardiomyopathy occurred with a usual dose of pegylated interferon-alpha. Clinicians should be aware of this potential complication when evaluating the ratio benefit/risk of treatment in patients with chronic hepatitis C infection.

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