Elevated Initial APRI Value Was Associated With SALD

Study Overview
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Brief Summary
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Sepsis, characterized by severe organ dysfunction related to a dysregulated immune response to infection, is often life-threatening in clinical settings. Sepsis can progress to multiple organ dysfunction syndrome (MODS), causing a great risk of mortality. As a vital immune and metabolic organ, liver often suffers damage in this process and often associated with severe adverse consequences. Compared to general sepsis population, sepsis-associated liver dysfunction (SALD) has a higher mortality, up to 68.6%. The aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), which can be calculated from conventional laboratory indicators, has long been used in the evaluation of liver damage and fibrosis in patients with hepatitis and nonalcoholic fatty liver disease. AST is a sensitive indicator of early liver function impairment. Additionally, PLT also plays a crucial role in sepsis-induced MODS through regulating inflammation, maintaining tissue integrity, and defending against infection. Study found that APRI was a good predictor of SALD occurrence in pediatric patients with sepsis. Furthermore, APRI has also been used to predict the prognostic in septic patients with no history of chronic liver disease. We conducted a retrospective study based on data from the Medical Information Mart for Intensive Care IV version 2.2 (MIMIC-IV, v2.2) and our own hospital to explore the potential association of APRI with the occurrence of SALD in adult patients with sepsis. Furthermore, we also evaluated the performance of APRI in hypoxic hepatitis and sepsis induced cholestasis (SIC), which are two subtypes of SALD.

Detailed Description
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We included adult sepsis patients (≥18 years) as study participants, but only those who had data available for their first hospitalization and first ICU admission were enrolled in our study, if they had multiple admission records in the database. Exclusion criteria include: 1) all types of chronic liver disease; 2) viral hepatitis; 3) primary acute cholangiopathies; 4) cholecystitis; 5) hepatic infarction; 6) liver necrosis; 7) liver trauma; 8) length of ICU stay < 24 hours. Patients without simultaneous AST and PLT data in the first 24 hours after ICU admission were also excluded. The following indicators were extracted directly or derived from the database(MIMIC IV): age; weight; gender; comorbidity, including hypertension, old myocardial infarct, chronic heart failure, cerebrovascular disease, chronic pulmonary disease, chronic renal disease and diabetes; infection site, including blood, lung, skin and soft tissue, abdominal cavity and urinary tract; disease severity scores within the first day of ICU admission, including Acute Physiology Score III (APS III), Sequential Organ Failure Assessment (SOFA), Logistic Organ Dysfunction Score (LODS), Oxford Acute Severity of illness Score (OASIS) and Simplified Acute Physiology Score II (SAPS II); mean vital signs in first 24h, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), respiratory rate (RR), temperature and pulse oxygen saturation (SPO2); treatment received within the first day of ICU admission, including invasive ventilation, vasopressor therapy, renal replacement therapy and parenteral nutrition (PN) support; initial laboratory parameters, including white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell (RBC), red blood cell distribution width (RDW), platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), albumin, blood urea nitrogen (BUN), creatinine, bicarbonate, anionic gap, sodium, potassium, chloride, total calcium, glucose, prothrombin time (PT), partial prothrombine time (APTT), international normalized ratio (INR) and APRI; clinical outcome measures, including intensive care unit (ICU) length of stay (LOS), hospital LOS, ICU mortality, in-hospital mortality, and 30-day mortality. The disease severity scores, including APS III, SOFA, LODS, OASIS, SAPS II, are calculated using the SQL code provided by Johnson et al. APRI is calculated by (AST(IU/L)/ upper limits of normal)/PLT(k/uL)×100. Sepsis is diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Briefly, patients with confirmed or suspected foci of infectious and a concurrent SOFA≥2. SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL). Following the exclusion of ineligible patients, the data underwent a thorough examination, and extreme and erroneous values that failed logical checks were removed. Variables with missing data exceeding 30% of the sample size were excluded. For the remaining variables with missing values, the mean imputation method was applied to address them. We first used the MIMIC IV database to assess the correlation between APRI and the occurrence of SALD using association analysis. We then validated these results using our own data.

Official Title
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Elevated Initial APRI Value Was Associated With the Development of Sepsis-associated Liver Dysfunction in Adult Patients With Sepsis

Conditions
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Liver Dysfunction, Sepsis-associated Liver Dysfunction

Intervention / Treatment
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* Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio index


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult sepsis patients (≥18 years) Exclusion Criteria: all types of chronic liver disease; viral hepatitis; primary acute cholangiopathies; cholecystitis; hepatic infarction; liver necrosis; liver trauma; length of ICU stay < 24 hours; Patients without simultaneous AST and PLT data in the first 24 hours after ICU admission.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-SALD group<br>SALD did not occur in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. | Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio index<br>* All eligible patients were given antibiotics therapy, actively control infection source, as well as other supportive therapy to maintain organ function.<br>|
| SALD group<br>SALD was occured in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL). | Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio index<br>* All eligible patients were given antibiotics therapy, actively control infection source, as well as other supportive therapy to maintain organ function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of SALD | Whether SALD occurs | 30 days after ICU admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | Death at 30 days after ICU | 30 days after ICU admission |