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.

Markers of obesity in Danish pediatric liver transplantation recipients.

BACKGROUND: Long-time survivors of pediatric liver transplantation have an increased incidence of the metabolic syndrome. Adult recipients have an increased risk of post-transplantation obesity; however, pediatric data are limited. METHODS: The study included 42 recipients of pediatric liver transplantation in Denmark, transplanted between 1990 and 2014. The study participants were examined with anthropometric measures, dual-energy X-ray scans and blood samples. From the anthropometric measures, body mass index (BMI) and BMI standard deviation score (SDS) were calculated. From the dual-energy X-ray scans, fat percent was assessed, and body fat mass index (BFMI) was calculated. RESULTS: The median age was 17.4 years (range 4.1-38.9) at the time of the study, and the median time since transplantation was 8.5 years (range 0.4-23.9). The prevalence of overweight and obesity was 31.0% based on BMI SDS (age below 18) and BMI (age 18 and above). When compared to the participants with normal weight, the participants with overweight and obesity had a higher BFMI (9.29 vs 5.57 kg/m2 , p < .001) and fat percent (38.35% vs 29.50%, p = .006). They had higher levels of total cholesterol (4.3 vs 3.6 mmol/L, p = .023) and low-density lipoprotein (2.5 vs 1.7, p = .015), and had had longer time since transplantation (15.6 vs 8.5 years respectively, p = .045). CONCLUSIONS: Long-time survivors of pediatric liver transplantation have a higher BMI or BMI SDS than the general pediatric population. The obesity is characterized by a higher BFMI, fat percent, and cholesterols levels, when compared to recipients without overweight or obesity.

Severe acute hepatitis and acute liver failure of unknown origin in children: a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022.

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3-5, 0-2 and 3-5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0-8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise.

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] µmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 µmol/L (P = 0.05) tended to be associated with improved NLS. CONCLUSIONS: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

Secular change in adult stature has come to a halt in northern Europe and Italy.

AIM: To investigate whether the increase in adult stature in European countries is continuing. METHODS: The secular trend in growth after 1990 for various European countries was assessed by national conscript data. RESULTS: In Scandinavia and the Netherlands, the height has reached a plateau at 179-181 cm, and in Italy a plateau at 174 cm. In Belgium, Portugal and Spain, height continued to increase. CONCLUSION: Only in the northern European countries and Italy height has ceased to increase.