De Ritis ratio and cardiovascular disease: evidence and underlying mechanisms

Aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio) has been used as a marker of alcohol-related liver disease, liver fibrosis and muscle disease. This article reviewed the literature on the association of De Ritis ratio with cardiovascular disease (CVD). Recent studies support an association between elevated De Ritis ratio and prognosis of patients with diabetes mellitus, cancers, diseases characterized by multiorgan failure, CVD, stroke and corona virus disease (COVID)-19. Elevated De Ritis ratio may indicate increased cardiometabolic risk associated with overt or occult hepatic and extrahepatic diseases and may be a metabolic trait indicating abnormalities at the level of basic metabolism that foresees the development of future metabolic diseases. De Ritis ratio correlates positively with age, female sex, C-reactive protein and impaired renal function and inversely with diabetes mellitus, obesity and metabolic syndrome. Epidemiological studies suggest an association of elevated De Ritis ratio with CVD and strongly support an association between elevated De Ritis ratio and increased risk for all-cause and CVD-related mortality. The strength and direction of the association between De Ritis ratio and cardiovascular risk factors cannot explain the association between De Ritis ratio and CVD or CVD mortality. Elevated De Ritis ratio may represent cardiometabolic risk that is not mediated (or poorly mediated) by traditional risk factors and may be seen as an emerging nonstandard marker of cardiometabolic risk. De Ritis ratio requires standardization in terms of reference range and interpretation. Future epidemiological, clinical and laboratory (biochemical) studies are required to further investigate De Ritis ratio as a marker of cardiometabolic risk and CVD. © Journal of Laboratory and Precision Medicine. All rights reserved.

Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Recently, stroke prognosis estimation has received much attention. This study investigates the prognostic role of aspartate transaminase/alanine transaminase (De Ritis, AAR), alkaline phosphatase/alanine transaminase (ALP/ALT), and aspartate transaminase/alkaline phosphatase (AST/ALP) ratios in acute ischemic stroke (AIS). METHODS: This retrospective cohort study involved patients who experienced their first-ever AIS between September 2019 and June 2021. Clinical and laboratory data were collected within the first 24 hours after admission. Functional and mortality outcomes were evaluated 90 days after hospital discharge in clinical follow-up. Functional outcome was assessed by a modified Rankin Scale (mRS). The correlation between the laboratory data and study outcomes was evaluated using univariate analysis. In addition, regression models were developed to evaluate the predictive role of AST/ALP, ALP/ALT, and AAR ratios on the study outcomes. RESULTS: Two hundred seventy-seven patients (mean age 69.10 ± 13.55, 53.1% female) were included. According to univariate analysis, there was a weak association between 3-months mRS, and both AST/ALT (r = 0.222, P < 0.001), and AST/ALP (r = 0.164, P = 0.008). Subsequently, higher levels of these ratios and absolute values of AST, ALT, and ALP were reported in deceased patients. Based on regression models adjusted with co-variable (age, gender, underlying disease, and history of smoking) AST/ALT and AST/ALP ratios had a significant independent association with 3-month mRS (CI:1.37-4.52, p = 0.003, and CI: 4.45-11,547.32, p = 0.007, respectively) and mortality (CI: 0.17-1.06, adjusted R2 = 0.21, p = 0.007, and CI: 0.10-2.91, p = 0.035, adjusted R2 = 0.20, respectively). CONCLUSIONS: Elevated AST/ALP and AAR ratios at admission were correlated with poorer outcomes at 3 months in patients with first-ever AIS. Prospective studies in larger cohorts are required to confirm our findings and to evaluate further whether the AST/ALP and De Ritis ratios may represent a useful tool for determining the prognosis of AIS patients.

The Elevated De Ritis Ratio on Admission Is Independently Associated with Mortality in COVID-19 Patients.

Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.

A Linear Relationship Between De Ritis Ratio and Mortality in Hospitalized Patients With COVID-19: A Secondary Analysis Based on a Large Retrospective Cohort Study

Background and aims Although some studies have identified a possible link between the De Ritis ratio and the mortality of patients with COVID-19, the predictive value and the optimal cut-value remain unclear. This study aimed to explore the correlation between the De Ritis ratio and mortality in hospitalized COVID-19 patients. Methods The data for this cohort study came from a retrospective cohort study that was carried out in a medical system in New York City. The primary outcome was the in-hospital mortality of included patients. The researchers ran multivariate Cox regression analyses, curve fitting, and subgroup analysis to support our findings. Overall survival in different De Ritis ratio groups was plotted as Kaplan–Meier survival curves. Results The study enrolled 4371 participants with COVID-19 from 1 March 2020 to 16 April 2020. The overall mortality was 24.8% (1082/4371). The curve fitting analyses indicated that the De Ritis ratio has a positive linear connection with mortality in COVID-19 patients. After adjusting for all covariates, participants with a De Ritis ratio ≥ 2 exhibited 1.29 times the risk of in-hospital mortality compared with those with a De Ritis ratio < 1 (HR 1.29, 95% CI 1.02–1.62, p=0.031). The P for trend was<0.05 for all models. Patients in the group with a De Ritis ratio ≥ 2 experienced the shortest survival time in the Kaplan–Meier survival analysis. Conclusion A higher baseline De Ritis ratio is correlated with a corresponding higher mortality among hospitalized people with COVID-19.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19). Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC). Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p < 0.001; I 2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p < 0.001; I 2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p < 0.001; I 2: 35.8%]. It has a sensitivity of 55% (36-73), specificity of 71% (52-85), PLR 1.9, NLR.63, DOR of 3 (2-4), and AUC of.67 (0.63-0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated. Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19. Systematic Review Registration: PROSPERO ID: CRD42020216634.

The AST/ALT Ratio (De Ritis Ratio) Represents an Unfavorable Prognosis in Patients in Early-Stage SFTS: An Observational Cohort Study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), a widely prevalent infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) that carries with it a high mortality rate, has emerged to be a public health concern. This study aimed to investigate the epidemiological and clinical characteristics of patients infected with SFTSV, seeking novel prognostic risk factors for SFTS. METHODS: In this retrospective and cross-sectional study, confirmed SFTS patients from the First Affiliated Hospital of Anhui Medical University were enrolled from September 1, 2019, to December 12, 2020. Cases were analyzed for epidemiological, demographic, clinical, and laboratory data. Logistic regression models were used to assess the association between predictors and outcome variables. A generalized additive mixed model (GAMM) was conducted to analyze the trending shift of aspartate aminotransferase/alanine transaminase-ratio (AST/ALT-ratio) and platelet (PLT) in SFTS patients treated with ribavirin. p values ≤ 0.05 were considered statistically significant. RESULTS: Clinical and laboratory results of 107 hospitalized patients with SFTSV infection were retrospectively described. The mean age at onset of disease was 60.38 ± 11.29 years old and the ratio between male and female was 1:1.2. Fever and thrombocytopenia are hallmark features of SFTS. Furthermore, multiple cases also experienced neurological complications, gastrointestinal/skeletal muscle symptoms together with other non-specific clinical manifestations; laboratory dataset outcomes reported dysregulated levels for routine blood biomarkers, coagulation function, and biochemistry. Overall, 107 patients were segregated into two groups according to patient condition at the clinical endpoint (survivors/non-survivors). SFTS survivors had a higher level of PLT- counts, total protein (TP), and estimated glomerular filtration rate (eGFR), while levels of activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (D-D), fibrinogen degradation products (FDP), ALT, AST, AST/ALT-ratio, creatinine (Cr), creatine phosphokinase (CK) and procalcitonin (PCT) was higher in non-survivors. Results from univariate Cox regression revealed that elevated levels of FDP, TT, AST/ALT-ratio, PCT, as well as decreased eGFR level and presence of central nervous system symptoms (CNS), were significant predictors for SFTS prognostic, results from multivariate logistic regression analysis in three adjusted models showed AST/ALT-ratio and PCT were independent risk factors for the prognosis of SFTS patients. Kaplan-Meier survival analysis showed that SFTS patients with AST/ALT-ratio >2.683 were associated with a shorter futime (means survival time), therefore indicating an unfavorable prognosis. Treatment with ribavirin could increase PLT count while decreasing AST/ALT-ratio within SFTS patients. CONCLUSION: SFTS is an emerging infectious disease, possibly leading to multiple-organ injury; AST/ALT-ratio was an independent risk factor for the prognosis of SFTS patients. Further investigation should be performed in order to gain more knowledge on this disease and guide clinical management.

De ritis ratio and neutrophil-to-lymphocyte ratio in the diagnosis of COVID-19

Aim: The outbreak of the novel coronavirus disease (COVID-19) has been affecting the world day by day. The definitive diagnosis of COVID-19 is made using the real-time polymerase chain reaction (RT-PCR) method. Although the RT-PCR method is the gold standard for confirming infection, it requires a specialized laboratory, expensive equipment, and trained personnel. Thus, simple and alternative laboratory tests are needed to predict PCR positivity and disease. Material and Methods: We analyzed laboratory parameters of 147 patients who were hospitalized with a pre-diagnosis of COVID-19 and sent RT-PCR samples. Of these, 76 tests were positive and 71 were negative. In addition to routine laboratory parameters, we also examined ratios derived from them, such as the De Ritis ratio (AST to ALT ratio) and Neutrophil-to-Lymphocyte Ratio (NLR). We investigated whether these parameters can predict the positivity or negativity of the PCR test. Results: CRP, D-dimer, Ferritin, AST values, NLR, and De Ritis ratio were found to be significantly higher in the PCR-positive group. It was observed that the lymphocyte count was lower in the positive group. Discussion: Our results suggest that routine laboratory tests that can be performed easily may also have the potential to predict COVID-19 positivity and negativity. These parameters can especially be used as an alternative in areas with a shortage of laboratories, equipment and personnel for PCR testing. Combining some hematological parameters and specific ratios derived from hematological parameters can help in identifying false positive/negative RT-PCR tests.

The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients.

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID-19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in-hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID-19) admitted to three COVID-19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91-1.64 vs 1.67; IQR: 1.38-1.97, P = .002) whilst there were no significant between-group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603-0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan-Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05-5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in-hospital mortality in COVID-19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.

De Ritis ratio and biochemical parameters in COVID-19 patients.

BACKGROUND: The study aimed to examine some biochemical test parameters and De Ritis ratio in COVID-19 patients, considering age and gender. METHOD: The study was performed on patients with real-time polymerase chain reaction and computed tomography lung diagnosis. The relationship between lactate dehydrogenase, creatine kinase (CK), creatine kinase-MB, alanine aminotransferase, aspartate aminotransferase and De Ritis ratio were analysed in the first blood samples of the patients. The difference between gender was also compared with the independent sample t-test. Alpha value was accepted <0.05. RESULTS: The De Ritis was significantly higher in females (p = .040). The De Ritis ratio was associated with CK in both gender. There was no significant difference in the biochemical parameters according to gender. CONCLUSION: The De Ritis ratio appears to be a parameter that can be used in COVID-19 patients. However, more detailed and comprehensive studies including the symptoms of patients are needed.