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A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease.

ABSTRACT: The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.

SUBMITTER: Aberg F

PROVIDER: S-EPMC8183175 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveRecent evidence has revealed that the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) may be closely associated with metabolic syndrome and insulin resistance. However, it is unclear whether the AST/ALT ratio correlates with prediabetes risk. The aim of our study was to examine the association between AST/ALT ratios and the risk of prediabetes among a large cohort of Chinese subjects.MethodsThis retrospective cohort study recruited 75204 Chinese adults with normoglycemia at baseline who underwent physical examinations at the Rich Healthcare Group from 2010 to 2016. The AST/ALT ratio at baseline was the target independent variable, and the risk of developing prediabetes during follow-up was the dependent variable. Cox proportional-hazards regression was used to evaluate the independent association between the AST/ALT ratio and prediabetes. This study identified nonlinear relationships by applying a generalized additive model (GAM) and smooth curve fitting. In order to assess the robustness of this study, we performed a series of sensitivity analyses. Moreover, we performed a subgroup analysis to evaluate the consistency of the association in different subgroups. Data from this study have been updated on the DATADRYAD website.ResultsThe AST/ALT ratio was negatively and independently related to the prediabetes risk among Chinese adults (HR: 0.76, 95% CI: 0.75-0.84, P<0.0001) after adjusting demographic and biochemical covariates. Furthermore, a nonlinear relationship between the AST/ALT ratio and the risk of developing prediabetes was found at an inflection point of 1.50 for the AST/ALT ratio. When the AST/ALT ratio was to the left of the inflection point (AST/ALT ratio ≤ 1.50), the AST/ALT ratio was negatively related to the prediabetes risk (HR:0.70, 95%CI: 0.65-0.76, P<0.0001). In contrast, the relationship tended to be saturated when the AST/ALT ratio was more than 1.50 (HR: 1.01, 95%CI: 0.89-1.15, P=0.8976). Our findings remained robust across a range of sensitivity analyses. Subgroup analysis revealed that other variables did not alter the relationship between the AST/ALT ratio and prediabetes risk.ConclusionThis study revealed that AST/ALT ratio was negatively and independently associated with prediabetes risk among Chinese participants. The relationship between the AST/ALT ratio and prediabetes risk was nonlinear, and AST/ALT ratio ≤ 1.50 was strongly inversely correlated with prediabetes risk.

Project description:BackgroundThe aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio has been shown to be associated with poor clinical outcomes across various patient groups. However, little is unclear about the association between the two in critically ill older patients. Therefore, we aim to investigate the association of the AST/ALT ratio with hospital mortality in this special population.MethodsIn this retrospective cohort study, we extracted elderly patients (age ≥ 65 years) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was in-hospital mortality. The association between the AST/ALT ratio and hospital mortality was studied using univariable and multivariable Cox regression analysis, as well as restricted cubic splines (RCS). Survival analysis was performed using the Kaplan-Meier (KM) method according to the AST/ALT ratio.ResultsAmong the 13,358 eligible patients, the mean age was 77.6 years, 7,077 patients (52.9%) were male, and 2,511 patients (18.8%) died in hospital. The AST/ALT ratio was found to be independently associated with in-hospital mortality (HR = 1.05, 95% CI: 1.01-1.09, P = 0.022) after adjusting for potential confounders. Furthermore, a non-linear relationship and saturation effect were observed between them, with the inflection point being 1.80. When the AST/ALT ratio was less than 1.80, we found that every 1 unit increase in the AST/ALT ratio resulted in a 39% increased risk of in-hospital mortality (HR = 1.39, 95% CI: 1.18-1.64, P < 0.001). However, when the AST/ALT ratio was greater than 1.80, the association became saturated (HR = 1.01, 95% CI: 0.96-1.07, P = 0.609). Sensitivity and subgroup analyses showed the results were robust.ConclusionIn critically ill older patients, the association between the AST/ALT ratio and in-hospital mortality was non-linear and showed a saturation effect. An elevated AST/ALT ratio was significantly associated with increased in-hospital mortality when the AST/ALT ratio was less than 1.80.

Project description:BackgroundAccumulating evidence has revealed that the aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio is a promising novel biomarker for insulin resistance (IR) and metabolic diseases. However, research on the association between the AST/ALT ratio and the incidence of diabetes progressing from prediabetes remains lacking. Herein, this study aimed to evaluate the relationship between the baseline AST/ALT ratio and risks of diabetes in patients with prediabetes.MethodsThis was a retrospective cohort study involving a total of 82,683 participants across 32 regions and 11 cities in China from 2010 to 2016. Data was obtained based on the DATADRYAD database from the health check screening program. Participants were stratified according to the interquartile range of the AST/ALT ratio (groups Q1 to Q4). The Cox proportional hazard model and smooth curve fitting were used to explore the relationship between the baseline AST/ALT ratio and the risk of diabetes in prediabetic patients. In addition, subgroup analysis was used to further validate the stability of the results.ResultsThe mean age of the selected participants was 49.9 ± 14.0 years, with 66.8% of them being male. During the follow-up period 1,273 participants (11.3%) developed diabetes progressing from prediabetes during the follow-up period. Participants who developed diabetes were older and were more likely to be male. The fully-adjusted Cox proportional hazard model revealed that the AST/ALT ratio was negatively associated with the risk of diabetes in prediabetic patients (HR = 0.40, 95% CI: 0.33 to 0.48, P < 0.001). Higher AST/ALT ratio groups (Q4) also presented with a lower risk of progressing into diabetes (HR = 0.35, 95% CI: 0.29 to 0.43, P < 0.001, respectively) compared with the lowest quintile group (Q1). Through subgroup analysis and interaction tests, it was found that the association stably existed in all subgroup variables, and there were a stronger interactive effects in people with age < 45 years, and TG ≤ 1.7 mmol/L in the association between AST/ALT ratio and diabetes incidences in patients with prediabetes (P for interaction < 0.05).ConclusionAccording to our study, a higher AST/ALT ratio is associated with a lower risk of progressing into diabetes from prediabetes. Regular monitoring of AST/ALT ratio dynamics and corresponding interventions can help prevent or slow prediabetes progression for diabetes.

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A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease.

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