Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis.

BACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC). AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications. METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed. RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score. CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Global prevalence, incidence, and outcomes of alcohol related liver diseases: a systematic review and meta-analysis.

BACKGROUND: Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes of ARLD. METHODS: Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to May 31, 2022. The language was restricted to English or Chinese. According to the criteria, articles describing the basic characteristics of the population were selected. Two reviewers extracted the data independently. RESULTS: A total of 372 studies were identified: 353 were used for prevalence analysis, 7 were used for incidence analysis, and 114 were used to for outcome analysis. The prevalence of ARLD worldwide was 4.8%. The prevalence in males was 2.9%, which was higher than female (0.5%). Among the ethnic groups, the percentage was highest in Caucasians (68.9%). Alcoholic liver cirrhosis comprised the highest proportion in the disease spectrum of ARLD at 32.9%. The prevalence of ascites in ARLD population was highest (25.1%). The ARLD population who drinking for > 20 years accounted for 54.8%, and the average daily alcohol intake was 146.6 g/d. About 59.5% of ARLD patients were current or former smokers, and 18.7% were complicated with hepatitis virus infection. The incidence was 0.208/1000 person-years. The overall mortality was 23.9%, and the liver-related mortality was 21.6%. CONCLUSION: The global prevalence of ARLD was 4.8% and was affected by sex, region, drinking years, and other factors. Therefore, removing the factors causing a high disease prevalence is an urgent requisite. TRIAL REGISTRATION: PROSPERO Nr: CRD42021286192.

NLRP3 inflammasome is involved in nerve recovery after sciatic nerve injury.

The activation of the inflammasome plays an important role in the central nervous system. However, only a few studies have investigated the effects of inflammasome activation in the peripheral nerve, especially in the sciatic nerve, and the mechanism of this activation remains elusive. Moreover, how interleukin-1 beta (IL-1ß) is produced after sciatic nerve injury is also unknown. In our study, we aimed to investigate whether the nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is activated after sciatic nerve injury and to explore its role in sciatic nerve injury. The results of immunoblotting and immunofluorescence microscopy indicate that the NLRP3 inflammasome was activated after sciatic nerve injury in wild-type (WT) mice, as demonstrated by upregulated inflammasome-related components, e.g., NLRP3, procaspase-1 and ASC. Furthermore, upregulated inflammasome-related components cis-cleavage precursor IL-1ß (proIL-1ß) and precursor interleukin-18 (proIL-18) to IL-1ß and IL-18, contributing to the inflammatory response. Consequently, the inflammatory response after sciatic nerve injury in NLRP3 knockout (NLRP3-KO) mice was less severe than that in WT mice. Moreover, NLRP3-KO mice exhibited an increased sciatic functional index (SFI), which was determined by footprint analysis, suggesting that NLRP3 deficiency is beneficial to sciatic nerve recovery after injury. Therefore, our results indicate that NLRP3 is involved in the recovery from sciatic nerve injury and mediates the production of inflammatory factors, such as IL-1ß, after sciatic nerve injury.