Background: Liver cirrhosis is a major health concern. Herein, we aimed to estimate the incidence, prevalence, and mortality of liver cirrhosis caused by specific etiologies for 204 countries and territories. Materials and Methods: The data were retrieved from the Global Burden of Disease Study 2019. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate, and estimated annual percentage changes were used to estimate the trends in incidence, prevalence, and mortality of liver cirrhosis by sex, region, country, and etiology between 2009 and 2019. Results: From 2009 to 2019, the incident cases of liver cirrhosis increased by 16.7%, from 1.8 million (95% uncertainty interval: 1.5–2.1) to 2.1 million (1.7–2.5), and the prevalent cases increased from 1378.3 million (1275.1–1498.8) to 1691.0 million (1560.9–1845.5). Liver cirrhosis contributed to nearly 1.5 million (1.4–1.6) deaths in 2019, nearly 0.2 million more than in 2009. However, the age-standardized death rate fell from 20.71 (19.79–21.65) per 100,000 population in 2009 to 18.00 (16.80–19.31) per 100,000 population in 2019. In terms of sex, males showed higher ASIR, ASPR, and age-standardized death rate than females. Among the etiologies, the ASIR and ASPR of NAFLD increased markedly, and there was also a modest increase in ASIR and ASPR for HCV and alcohol use. In contrast, the ASIR and ASPR of HBV decreased considerably. Conclusions: Our finding suggests an increasing burden of liver cirrhosis worldwide but a declining attributed death. A high prevalence and still rising trend of NAFLD and alcohol use-etiology were found in patients with cirrhosis globally, although variation was found between regions/countries. These data indicate that efforts to reduce the associated burden need to be improved. Export

Background and Aims: Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation accompanied by defective anti-bacterial immunity. The role of neutrophils in immune derangement of ACLF has not been fully elucidated. This study is aimed to characterize the role of circulating neutrophils in HBV-related ACLF patients.Methods: Quantitative, phenotypic, transcriptomic, and functional alterations of circulating neutrophils were compared in ACLF and non-ACLF subjects and analyzed for associations with short-term outcomes. Interventional experiments were performed to test the impact on ACLF-patient neutrophil function in vitro.Results: Circulating absolute neutrophil count was significantly increased in patients with ACLF and was an independent risk factor for 28-day mortality. ACLF-patient neutrophils differentially expressed a panel of surface markers (include TLR-1, TLR-2, TLR-4, CEACAM-1 and FPR1), as well as a distinct transcriptomic signature. ACLF-neutrophils displayed significantly impaired phagocytosis but an increased capacity to form neutrophil extracellular traps (NETs), which was more pronounced in patients with poor outcome. Healthy neutrophils mimicked functional characteristics of ACLF counterpart after co-cultured with plasma from ACLF patients. The oxidative burst and cytokine production capacities remained unchanged. Plasma GM-CSF, IL-6, IL-8, IL-10, and IP-10 levels, as well as lipopolysaccharide (LPS) concentration, were markedly elevated in ACLF patients but not DAMP molecules HMGB-1 and HSP70. Finally, a glycolysis inhibitor, 2-deoxy-glucose, reduced NET formation of ACLF patients’ neutrophils.Conclusions: Circulating ACLF-patient neutrophils exhibit alterations in number, phenotype, gene expression and function, which was associated with poor outcome and shaped by the ACLF circulatory environment. Inhibiting glycolysis can reverse neutrophil dysfunction in ACLF patients.