The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Diminished Non-Classical Monocytes in the Blood Associate with Disease Severity in Alcoholic Hepatitis

Elisabeth Busk Rasmussen,1 Lotte Lindgreen Eriksen,2 Stinne Ravn Greisen,1 Anne Louise Hansen,1 Mikkel Carstensen,1 Thomas Damgaard Sandahl,2 Sidsel Støy,2 Tue Wenzel Kragstrup1,3 1Department of Biomedicine, Aarhus University, Aarhus, Denmark; 2Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 3Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, DenmarkCorrespondence: Tue Wenzel KragstrupDepartment of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, Aarhus C, DK-8000, DenmarkTel +4587167265Email [email protected]: Alcoholic hepatitis (AH) holds a high mortality, and vast macrophage infiltration of the liver is involved in the progressive liver injury. No efficient medical treatment exists, and macrophages may be a future treatment target. Here, we examine associations between non-classical monocyte subsets and cell surface markers of migration with disease activity in patients with severe AH.Methods: We analyzed samples from two cohorts of patients with AH. Cohort 1 included 15 AH patients, followed for 30 days, and 8 healthy controls (HCs). Cohort 2 included 23 AH patients, followed for 90 days, and 9 HCs. Peripheral blood mononuclear cells (PBMCs) from both cohorts were analyzed by flow cytometry. Liver biopsies from cohort 2 were analyzed by RNA sequencing.Results: Circulating non-classical monocytes in all but absent in patients with AH compared to HC in both cohorts (both p< 0.0001). The frequency of non-classical monocytes was significantly associated with Maddrey’s discriminant function (mDF) (r=− 0.79, p=0.0008, cohort 1), Child–Pugh score (CP) (r=− 0.56, p=0.03, cohort 1), Model for End-Stage Liver Disease (MELD) (r=− 0.54, p=0.02, cohort 2) and C-reactive protein (CRP) (r=− 0.51, p=0.027, cohort 2). The surface expression of CD11b was increased on non-classical monocytes in patients with AH compared to HC (p< 0.0001) (cohort 1). The mRNA expression of CD11b was increased in liver biopsies in patients with AH compared to HC (cohort 2) (p< 0.0001).Conclusion: In this study, we describe an almost complete depletion of circulating non-classical monocytes in the blood in two independent cohorts of patients with AH, which may be associated with a possible harmful recruitment of these cells to the liver. These results contribute to a better understanding of the disease, which hopefully can lead to therapies that target the acute inflammatory response leading to severe AH.Keywords: monocytes, non-classical, alcoholic hepatitis, CD11b, CCR2, CX3CR

Mass spectrometry characterization of circulating human serum albumin microheterogeneity in patients with alcoholic hepatitis.

Human serum albumin (HSA) is the most abundant plasma protein, endowed with several biological properties unrelated to its oncotic power, such as antioxidant and free-radicals scavenging activities, binding and transport of many endogenous and exogenous substances, and regulation of endothelial function and inflammatory response. These non-oncotic activities are closely connected to the peculiarly dynamic structure of the albumin molecule. HSA undergoes spontaneous structural modifications, mainly by reaction with oxidants and saccharides; however, patients with cirrhosis show extensive post-transcriptional changes at several molecular sites of HSA, the degree of which parallels the severity of the disease. The present work reports the development and application of an innovative LC-MS analytical method for a rapid and reproducible determination of the relative abundance of HSA isoforms in plasma samples from alcoholic hepatitis (AH) patients. A condition of severe oxidative stress, similar to that observed in AH patients, is associated with profound changes in circulating HSA microheterogeneity. More interestingly, the high resolution provided by the analytical platform allowed the monitoring of novel oxidative products of HSA never reported before