Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. Methods: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. Results: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0–30%), between 2016–2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15–56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. Conclusions: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. Lay summary: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years

Development and Validation of Hepamet Fibrosis Scoring System-a Simple, Non-invasive Test to Identify Patients With Nonalcoholic Fatty liver Disease With Advanced Fibrosis

BACKGROUND & AIMS: Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. METHODS: We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n=768) and validated the system using patients from Cuba (n=344), Italy (n=288), France (n=830), and China (n=232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. RESULTS: Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P=.0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P<.05). CONCLUSIONS: Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis

Skeletal carbonate mineralogy of Scottish bryozoans

This paper describes the skeletal carbonate mineralogy of 156 bryozoan species collected from Scotland (sourced both from museum collections and from waters around Scotland) and collated from literature. This collection represents 79% of the species which inhabit Scottish waters and is a greater number and proportion of extant species than any previous regional study. The study is also of significance globally where the data augment the growing database of mineralogical analyses and offers first analyses for 26 genera and four families. Specimens were collated through a combination of field sampling and existing collections and were analysed by X-ray diffraction (XRD) and micro-XRD to determine wt% MgCO3 in calcite and wt% aragonite. Species distribution data and phylogenetic organisation were applied to understand distributional, taxonomic and phylo-mineralogical patterns. Analysis of the skeletal composition of Scottish bryozoans shows that the group is statistically different from neighbouring Arctic fauna but features a range of mineralogy comparable to other temperate regions. As has been previously reported, cyclostomes feature low Mg in calcite and very little aragonite, whereas cheilostomes show much more variability, including bimineralic species. Scotland is a highly variable region, open to biological and environmental influx from all directions, and bryozoans exhibit this in the wide range of within-species mineralogical variability they present. This plasticity in skeletal composition may be driven by a combination of environmentally-induced phenotypic variation, or physiological factors. A flexible response to environment, as manifested in a wide range of skeletal mineralogy within a species, may be one characteristic of successful invasive bryozoans

Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation

Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. Serum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. Our preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost

De Novo Donor-Specific Anti-Human Leukocyte Antigen Antibody Detection in Long-Term Adult Liver Transplantation

Information about the consequences of de novo donor-specific anti-human leukocyte antigen (DSA) antibody development in the long term after adult liver transplantation (LT) is scarce. We conducted a cross-sectional study in LT patients with a follow-up of at least 6 years. A total of 28 adult LT patients were included, with a median follow-up of 77 months (range, 63 to 96) and without preformed anti- human leukocyte antigen (HLA) antibodies prior to LT. The anti-HLA identification was performed with LABScreen Single Antigen, whereas the ability to fix the complement was demonstrated with C1q test (One Lambda). In both assays, a value >3.500 mean fluorescence intensity (MFI) was considered positive. The anti-HLA antibody specificities were compared with donor HLA antigens to confirm them as DSA. Hepatic fibrosis was assessed by transient elastography. In 5 patients (17.8%), de novo DSA were detected, all them against DQ locus. In all of these cases (100%) the complement fixation was confirmed by C1q binding. The grade of hepatic fibrosis in de novo DSA patients was significantly higher compared with No-DSA patients (13.2 ± 9.2 KPa vs 7.3 ± 3.7 KPa; P = .02). It is noteworthy that in both groups of patients the levels of liver function tests (LFT) at the time of the study were normal or near the normal range with no difference between patients with or without de novo DSA. Our preliminary results are consistent with those previously demonstrated in pediatric LT, where de novo DSA production and humoral response could contribute to the liver fibrosis observed in the long term after LT in pediatric patients with normal or near-normal LFT