Liver Fibrosis Indices Predict the Severity of SARS-CoV-2 Infection

Abstract

Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients’ individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients.

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

“…These increases in liver fibrosis scores among SARS‐CoV‐2‐infected patients may reflect liver fibrosis. However, previous studies have reported that liver fibrosis scores were lower at discharge compared with the time of admission in patients with COVID‐19, 23,25 a finding corroborated by the results of the present study.…”

“…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 .…”

“…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 .…”

“…[17][18][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][21][22][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 The increased liver fibrosis scores in SARS-CoV-2-infected patients without NAFLD may be attributable to liver injury due to COVID-19 rather than progression of liver fibrosis, as liver fibrosis scores in SARS-CoV-2-infected patients were lower at the time of discharge than on admission.…”