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A growing body of evidence now highlights a key role for systemic inflammation in altering behavior and mood in patients with liver disease. How inflammation occurring in the periphery in the context of liver disease, communicates with the brain to mediate changes in neurotransmission and thereby behavior is incompletely understood. Traditional routes of communication between the periphery and the brain involve neural (i.e. vagal afferent nerves) and humoral (blood-borne) pathways, with increased circulating levels of endotoxin and cytokines (especially Tumor Necrosis Factor a, TNFa) that occur during systemic inflammatory responses, as being primarily implicated in mediating signaling via these pathways. However, in recent years communication via peripheral immune-cell-to-brain and the gut-microbiota-to-brain routes have received increasing attention in the context of liver disease for their ability to modulate brain function, and generate a spectrum of symptoms ranging from fatigue and altered mood to overt Hepatic Encephalopathy (HE). In this review, we discuss periphery-to-brain communication pathways and their potential role in mediating systemic inflammationassociated alterations in behavior, that are in turn ultimately part of a spectrum of brain changes linked to the development of clinically apparent HE.

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INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS:The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS:The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC 5 23.9%; 95% CI: 24.4, 23.3) and morality rates (AAPC 5 24.7%; 95% CI: 25.6, 23.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021.DISCUSSION:PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.