Evaluation of FIB-4, NFS, APRI and Liver Function Tests as Predictors for SARS-CoV-2 Infection in the Elderly Population: A Matched Case-Control Analysis

Abstract

Several investigations have revealed that COVID-19 causes a significant death rate due to acute respiratory distress syndrome, alterations in the quantity of ACE2 receptor expression, or the intensity of cytokine storm. Similarly, patients with hepatic impairment that are co-infected with SARS-CoV-2 are more likely to display upregulations of ACE2 receptors and cytokine storm overload, which exacerbates hepatic impairment, potentially increasing the death rate. Moreover, it is expected that the aging population develops a higher degree of hepatic fibrosis in association with other comorbid conditions that are likely to influence the course of COVID-19. Therefore, this research was developed to describe the differences in liver test parameters in elderly individuals with COVID-19 in relation to other inflammatory markers and outcomes. This current observational single-center research followed a case-control design of elderly patients hospitalized for SARS-CoV-2 infection. The research was conducted at a tertiary emergency hospital in western Romania during a two-year period. There were 632 patients included in the analysis that were split into two equal groups matched 1:1 based on gender and body mass index. Three hundred sixteen patients made the group of cases with COVID-19 patients older than 65 years, while the other half were the 316 patient controls with COVID-19 that were younger than 65 years old. Disease outcomes showed a higher prevalence of ICU admissions (22.8% vs. 12.7%, p-value < 0.001) and in-hospital mortality (17.1% vs. 8.9%, p-value = 0.002) in the group of cases. Specific and non-specific liver biomarkers were identified as risk factors for mortality in the elderly, such as ALP (OR = 1.26), LDH (OR = 1.68), AST (OR = 1.98), and ALT (OR = 2.34). Similarly, patients with APRI and NFS scores higher than 1.5 were, respectively, 2.69 times and, 3.05 times more likely to die from COVID-19, and patients with FIB-4 scores higher than 3.25 were 3.13 times more likely to die during hospitalization for SARS-CoV-2 infection. Our research indicates that abnormally increased liver biomarkers and high liver fibrosis scores are related to a worse prognosis in SARS-CoV-2 infected individuals.

A nationwide study of liver disease hospitalizations during the coronavirus pandemic in the United States

“…This is also consistent with prior smaller studies that have been single‐center or single health system in design 10 . Higher scores on traditional non‐invasive liver scoring systems, such as APRI, FIB‐4, NFS, and MELD have also been shown to carry worse prognosis in patients infected with COVID‐19 in both patients with cirrhosis and independent of a diagnosis of liver disease 22–25 with a MELD score ≥ 18.5 predicting in‐hospital mortality with a 99% sensitivity and 100% specificity 26 . However, given the absence of laboratory data in the NIS, we were unable to validate these observations from prior studies.…”

Aspartate aminotransferase to platelet ratio index has utility as a biomarker of COVID‐19 severity in patients with nonalcoholic fatty liver disease

“…Accordingly, the APRI is more likely to have utility in predicting COVID‐19 severity in patients with NAFLD. Previous studies reported that serum AST levels were higher in patients with non‐chronic liver disease in the non‐survival group of COVID‐19 than in the patients in the survival group, 20 and APRI was associated with mortality in patients with non‐chronic liver disease with COVID‐19 3,20 . We believe that APRI predicts COVID‐19 severity in cases of non‐NAFLD as well as NAFLD, although the present study investigated only patients with NAFLD.…”

“…Previous several studies reported an association between COVID‐19 severity and liver fibrosis scores. However, the mechanisms underlying the association between liver fibrosis scores and COVID‐19 severity have yet to be fully elucidated 3,20–23 . A previous study reported that serum SARS‐CoV‐2 RNA levels were associated with COVID‐19 severity 35 .…”

“…SARS‐CoV‐2 then spread rapidly to neighboring states to become a global pandemic. To date, the WHO has identified more than 600 million cases of COVID‐19 worldwide, with more than 6 million deaths from COVID‐19 as of December 2022 3 . Obesity, hypertension, diabetes, chronic liver disease, renal disease, and heart disease are known risk factors for COVID‐19 mortality 4,5 …”

“…The use of noninvasive scoring systems based on platelet counts and serum liver enzyme levels in addition to patient demographics, such as the Fibrosis‐4 (FIB‐4) index and NAFLD fibrosis score (NFS), is recommended for predicting the risk of fibrosis progression in patients with NAFLD 17–19 . Several previous studies have reported that the FIB‐4 index, NFS, and aspartate aminotransferase (AST) to platelet ratio index (APRI) are useful biomarkers for evaluating the risk of mortality or disease severity among SARS‐CoV‐2‐infected patients without NAFLD 3,20–23 . However, liver injury has been reported in SARS‐CoV‐2‐infected patients, 15,24 which is thought to be associated with several factors, including direct liver injury caused by SARS‐CoV‐2, drug‐induced liver injury, hypoxia reperfusion dysfunction, and cytokine storm 15,24 .…”