Neutrophil to lymphocyte ratio (NLR) is widely used to assess inflammatory diseases. We performed a systematic review to explore the prognostic role of NLR for the assessment of liver fibrosis and cirrhosis. Areas covered: We searched the PubMed and EMBASE databases for the eligible papers which explored the association between NLR and liver fibrosis/cirrhosis or investigated the prognostic value of NLR in cirrhotic patients. Expert commentary: In accordance with assessment of liver fibrosis stage, we classified papers into four subgroups by etiology. For the patients with nonalcoholic fatty liver disease (NAFLD) there was a significant association between NLR and fibrosis stage and nonalcoholic fatty liver disease activity score (NAS), while NLR had a negative correlation with fibrosis stage for the patients with chronic hepatitis B (CHB). As for the patients with and chronic hepatitis C (CHC), NLR might not be significantly associated with fibrosis stage. Moreover, NLR seemed to be significantly useful for predicting outcomes in cirrhotic patients. Hence, NLR might be associated with liver fibrosis stage, especially in patients with NAFLD. Furthermore, NLR might be a useful biomarker for evaluating the prognosis in cirrhotic patients.

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Induced autophagy is protective against myocardial hypoxia/ischemia (H/I) injury, but evidence regarding the extent of autophagic clearance under H/I and the molecular mechanisms that influence autophagic flux has scarcely been presented. Here, we report that CD38 knockout improved cardiac function and autophagic flux in CD38 −/− mice and CD38 −/− neonatal cardiomyocytes (CMs) under H/I conditions. Mechanistic studies demonstrated that overexpression of CD38 specifically downregulated the expression of Rab7 and its adaptor protein pleckstrin homology domain-containing protein family member 1 (PLEKHM1) through nicotinamide adenine dinucleotide (NAD)dependent and non-NAD-dependent pathways, respectively. Loss of Rab7/PLEKHM1 impaired the fusion of autophagosomes and lysosomes, resulting in autophagosome accumulation in the myocardium and consequent cardiac dysfunction under H/I conditions. Thus, CD38 mediated autophagic flux blockade and cardiac dysfunction in a Rab7/PLEKHM1-dependent manner. These findings suggest a potential therapeutic strategy involving targeted suppression of CD38 expression.

Background and Aims. Hepatic encephalopathy (HE) is characterized by recurrence and poor quality of life. Acute-on-chronic liver failure (ACLF) mainly occurs in patients with chronic liver diseases and often presents with HE. Several predictive models have been proposed to predict the outcomes of these patients. Our study is aimed at identifying associated risk factors and the prognostic accuracies of predictive models in HE patients with or without ACLF. Methods. Patients with liver cirrhosis were retrospectively enrolled. Risk factors were evaluated by multivariate regression analyses. The predictive capabilities of models were calculated using the receiver operating characteristic (ROC) curve analyses and compared by the DeLong tests. Outcomes were defined as in-hospital mortality, HE severity, and ACLF occurrence. Results. In multivariate regression analyses, serum biomarkers neutrophil and total bilirubin (TBIL) were independently correlated with in-hospital death. Alanine aminotransferase (ALT) and blood urea nitrogen (BUN) were independent serum biomarkers associated with HE severity. Hemoglobin, TBIL, BUN, and international normalized ratio (INR) were significant indicators associated with ACLF incidence. For prediction of in-hospital mortality, Child-Pugh was superior to the others in the whole patients, while NLR showed the best capability in the ACLF group. Conclusion. In cirrhotic patients present with HE, BUN is a risk factor associated with HE severity and ACLF incidence. Child-Pugh and NLR scores may be effective prognosticators in patients with HE.