Etiology and Outcome of Adult and Pediatric Acute Liver Failure in Europe

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent. No systematic data on incidence, causes, and outcome of ALF across Europe are available. Via an online survey we reached out to European Reference Network Centers on rare liver diseases. Numbers and etiology of ALF cases during 2020 were retrieved and diagnostic and treatment availabilities assessed. In total, 455 cases (306 adult, 149 pediatric) were reported from 36 centers from 20 countries. Intoxication was the most common cause in adult and pediatric care. The number of cases with indeterminate etiology is low. Diagnostic tools and specific treatment options are broadly available within this network. This is the first approach to report on etiology and outcome of ALF in the pediatric and adult population in Europe. High diagnostic yield and standard of care reflects the expert status of involved centers.</p

Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure.

The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention. These, as well as additional clinical procedures will be the subject of these clinical practice guidelines

Experimental observation of the M1 scissors mode in 254^{254}No

International audienceWe present the first experimental evidence of the scissors mode in the superheavy nucleus 254No produced in the 208Pb(48Ca, ))254No reaction. The spectrum of γ rays emitted by the excited 254No nuclei shows an enhanced γ-ray yield for transition energies of ≈2.5 MeV. By measuring the linear polarization properties of the emitted γ rays, we confirm that the transitions in the enhancement region are predominantly of magnetic-dipole character, characteristic for the scissors mode. To further characterize the enhanced γ-ray yield, simulations of the electromagnetic decay of 254No were performed. The observed enhancement is reproduced by including an M1 component in the γ strength function with total strength . This is in good agreement with the integrated M1 strength from sum-rule estimates and new calculations within the quasi-particle random-phase approximation presented here. Our results provide a stringent test of phenomenological formulae for the scissors mode currently used in stellar nucleosynthesis calculations. We find that those formulae are not satisfactory, and we recommend using sum-rule estimates assuming a rigid-body moment of inertia instead for describing the scissors mode in superheavy nuclei. (Elsevier B.V.