Dataset Information

Circulating trimethylamine-N-oxide is associated with all-cause mortality in subjects with nonalcoholic fatty liver disease.

ABSTRACT:

Background and aims

Trimethylamine-N-oxide (TMAO), a gut microbiota-liver metabolite, has been associated with cardiometabolic disease. However, whether TMAO is associated with nonalcoholic fatty liver disease (NAFLD) and NAFLD-related health outcomes remains unclear. We aimed to investigate the association of TMAO with NAFLD and to assess the extent to which the association of TMAO with all-cause mortality is dependent on the presence of NAFLD in the general population.

Methods

We included 5292 participants enrolled in the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort study. Cox proportional-hazards regression analyses were performed to study the association of TMAO with all-cause mortality in subjects with and without a fatty liver index (FLI) ≥60, which was used as a proxy of NAFLD.

Results

During a median follow-up of 8.2 years, 307 subjects died, of whom 133 were classified with NAFLD. TMAO was positively and independently associated with baseline FLI (Std β 0.08, 95% CI 0.05, 0.11, P < .001). Higher TMAO was associated with increased risk of all-cause mortality in subjects with NAFLD, in crude analysis (hazard ratio [HR] per 1 SD, 2.55, 95% CI 1.60, 4.05, P < .001) and after full adjustment (_adj HR 1.90, 95% CI 1.18, 3.04, P = .008). Such an association was not present in subjects without NAFLD (crude HR 1.14, 95% CI 0.81, 1.71, P = .39; _adj HR 0.95, 95% CI 0.65, 1.39, P = .78).

Conclusion

This prospective study revealed that plasma concentrations of TMAO were associated with all-cause mortality in subjects with NAFLD, independently of traditional risk factors.

SUBMITTER: Flores-Guerrero JL

PROVIDER: S-EPMC8518486 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Circulating trimethylamine-N-oxide is associated with all-cause mortality in subjects with nonalcoholic fatty liver disease.

Flores-Guerrero Jose L JL Post Adrian A van Dijk Peter R PR Connelly Margery A MA Garcia Erwin E Navis Gerjan G Bakker Stephan J L SJL Dullaart Robin P F RPF

Liver international : official journal of the International Association for the Study of the Liver 20210608 10

<h4>Background and aims</h4>Trimethylamine-N-oxide (TMAO), a gut microbiota-liver metabolite, has been associated with cardiometabolic disease. However, whether TMAO is associated with nonalcoholic fatty liver disease (NAFLD) and NAFLD-related health outcomes remains unclear. We aimed to investigate the association of TMAO with NAFLD and to assess the extent to which the association of TMAO with all-cause mortality is dependent on the presence of NAFLD in the general population.<h4>Methods</h4>W ...[more]

PMID: 33993608

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Project description:ObjectiveSystemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD.MethodsData was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan-Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines.ResultsA total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47-2.37; p < 0.0001). After controlling for confounders, an increase in log2-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26-1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log2-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log2-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71-1.15, p = 0.419). However, a higher log2-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49-2.02, p < 0.001).Based on a study of US NAFLD patients, it was found that the baseline log2-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients.KEY MESSAGESUsing a large nationally representative survey of individuals among US adults, the study demonstrated that log2-SII was J-shaped and associated with all-cause death among individuals with NAFLD.Spline analyses demonstrated that the association between log2-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8.Higher log2-SII associated with poor survival in NAFLD.

Project description:ObjectivesSoluble CD163 (sCD163), a marker of Kupffer cell activation detectable in serum, correlates with inflammation and fibrosis in chronic viral hepatitis, but its role in nonalcoholic fatty liver disease is unknown. We hypothesized that sCD163 would correlate with nonalcoholic fatty liver disease activity and fibrosis.MethodsLiver biopsies and serum were obtained from 145 obese subjects undergoing gastric bypass surgery. Subjects were divided into four groups based on fibrosis stage and nonalcoholic fatty liver disease activity score (NAS); Group 1: F0, NAS=0; Group 2: F<2, 0<NAS<5; Group 3: NAS≥5, F<3; or Group 4: F≥3, any NAS. Serum sCD163 and the monocyte/macrophage marker sCD14 were measured by enzyme-linked immunosorbent assay. Relationships between sCD163, sCD14, fibrosis stage, and NAS were examined. Area under the receiver operating charateristic for the diagnosis of nonalcoholic steatohepatitis based on the Clinical Research Network definition was calculated.ResultssCD163 increased with progressive liver histology, with lowest values in normal histology and highest levels in those with nonalcoholic steatohepatitis and advanced fibrosis (Group 1: 552 ng/ml, Group 2: 721 ng/ml, Group 3: 803 ng/ml, and Group 4:1,031; P=0.001). sCD14 also differed significantly across groups (Group 1: 1,877 ng/ml, Group 2: 1632 ng/ml, Group 3: 1,706 ng/ml, and Group 4: 2111; P=0.008, respectively). sCD163 correlated with steatosis grade (P<0.001), lobular inflammation (P=0.033), and hepatocyte ballooning (P<0.001). In a multivariable ordered logistic regression model, there was a significant association between every 100 ng/ml increase in sCD163 and higher fibrosis stage, with an odds ratio of 1.16 (95% confidence interval 1.02-1.31), P=0.020. The odds ratios of the association between every 100 ng/ml increase in sCD163 and higher NAS was 1.17 (95% confidence interval 1.04-1.32), P=0.010. A sCD163-based predictive score demonstrated an area under the receiver operating charateristic of 0.70 (95% confidence interval: 0.58-0.82) for the diagnosis of nonalcoholic steatohepatitis. Soluble CD14 did not correlate with fibrosis stage or NAS.ConclusionsIn obese subjects, serum sCD163, but not sCD14, correlated with fibrosis stage and NAS. These data support a role for activated Kupffer cells in the pathogenesis of nonalcoholic steatohepatitis and fibrosis, and suggest potential clinical utility for assessment of sCD163 levels.

Dataset Information

Circulating trimethylamine-N-oxide is associated with all-cause mortality in subjects with nonalcoholic fatty liver disease.

Background and aims

Methods

Results

Conclusion

Publications

Circulating trimethylamine-N-oxide is associated with all-cause mortality in subjects with nonalcoholic fatty liver disease.

Similar Datasets

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