The impact of alcohol care teams on emergency secondary care use following a diagnosis of alcoholic liver disease - a national cohort study

Abstract Aims Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention, are limited. We analysed the impact of LD and OAC treatment in determining stroke, major bleeding, all-cause death and secondary bleeding outcomes. Methods A retrospective observational population-based cohort study. The study cohort is derived from the administrative health databases of Lombardy region (>10 million inhabitants), Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. AF and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical (ATC) codes. Primary study outcomes were stroke, major bleeding and all-cause death. Results Among 393,507 AF patients, 16,168 (4.1%) had concomitant LD. LD AF patients were significantly less treated with OAC independent of associated clinical characteristics (OR: 0.96, 95% CI: 0.92–0.98). Concomitant LD was found associated with an increased risk in all the study outcomes (HR: 1.18, 95% CI: 1.11–1.25 for stroke; HR: 1.57, 95% CI: 1.47–1.66 for major bleeding; HR: 1.41, 95% CI: 1.39–1.44 for all-cause death. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70–0.92), major bleeding (HR: 0.86, 95% CI: 0.74–0.99) and all-cause death (HR: 0.85, 95% CI: 0.80–0.90), with similar results according to several clinically relevant subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375–0.472). Conclusions In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant benefit/risk ratio, even in high-risk patient subgroups. Funding Acknowledgement Type of funding source: None

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Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease

Human Genomics ◽

10.1186/s40246-019-0251-1 ◽

2019 ◽

Vol 13 (1) ◽

Cited By ~ 4

Author(s):

Mohammed A. Assiri ◽

Hadi R. Ali ◽

John O. Marentette ◽

Youngho Yun ◽

Juan Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Alcoholic Liver Disease ◽

Mapk Pathway ◽

Early Stage ◽

Expression Profiles ◽

Ethanol Metabolism ◽

Metabolic Dysregulation ◽

Nicotinamide Mononucleotide ◽

The Impact

Abstract Background Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD. Methods To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis. Results Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression. Conclusions These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.

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