Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed

Presence and consequence of tooth periapical radiolucency in patients with cirrhosis

Lea Ladegaard Grønkjær,1 Palle Holmstrup,2 Søren Schou,3 Kristoffer Schwartz,4 Johanne Kongstad,2 Peter Jepsen,1,5 Hendrik Vilstrup1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, 2Section of Periodontology, Microbiology, and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, 3Section for Oral and Maxillofacial Surgery, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 4Department of Oral and Maxillofacial Surgery, 5Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: Periapical radiolucency is the radiographic sign of inflammatory bone lesions around the apex of the tooth. We determined the prevalence and predictors of periapical radiolucency in patients with cirrhosis and the association with systemic inflammation status and cirrhosis-related complications.Methods: A total of 110 cirrhosis patients were consecutively enrolled. Periapical radiolucency was defined as the presence of radiolucency or widening of the periapical periodontal ligament space to more than twice the normal width. Predictors of periapical radiolucency and the association with systemic inflammation markers and cirrhosis-related complications were explored by univariable and multivariable logistic regression analyses.Results: Periapical radiolucency was present in one or more teeth in 46% of the patients. Strong predictors were gross caries (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.43–6.79) and severe periodontitis (OR 3.98, 95% CI 1.04–15.20). Also old age (OR 1.10, 95% CI 1.01–1.19) and smoking (OR 3.24, 95% CI 1.02–17.62) were predictors. However, cirrhosis etiology (alcoholic vs nonalcoholic) or severity (Model of End-Stage Liver Disease score) were not predictors. The patients with periapical radiolucency had higher C-reactive protein (15.8 mg/L vs 8.1 mg/L, P=0.02) and lower albumin contents (25 g/L vs 28 g/L, P=0.04) than those without. Furthermore, the patients with periapical radiolucency had a higher prevalence of cirrhosis-related complications such as ascites, hepatic encephalopathy, and/or variceal ­bleeding (46% vs 27%, P=0.05).Conclusion: Periapical radiolucency is often present as an element of poor oral health status and likely has an adverse clinical significance, which should motivate diagnostic and clinical attention to the findings. Keywords: apical periodontitis, cirrhosis, C-reactive protein, inflammation status, MELD score, periapical radiolucenc