Impact of Fibrosis-4 Index Prior to COVID-19 on Outcomes in Patients at Risk of Non-alcoholic Fatty Liver Disease

Abstract

Background Severity of disease and outcomes in patient with COVID-19 has been associated with several risk factors tied to the metabolic syndrome. Aims We conducted a study with the objective of describing the association between the baseline Fibrosis-4 (FIB-4) index prior to SARS-CoV-2 infection and the severity of COVID-19 among patients at risk of non-alcoholic fatty liver disease (NAFLD). Methods This was a retrospective cohort study of patients with at least two risk factors for metabolic syndrome diagnosed with COVID-19. The main exposure of interest was FIB-4 index prior to infection, categorized into three previously validated age-specific levels. The main outcomes of interest were disease requiring hospitalization and in-hospital mortality. Results We included 373 patients [median age, 62 years; 194 male (52%); median number of metabolic syndrome risk factors, 3]. The median FIB-4 index was 1.10 (interquartile range 0.78–1.61). In models adjusting for diabetes mellitus and chronic kidney disease, patients with intermediate FIB-4 index had 67% higher odds of hospitalization compared to those in the low category {odds ratio (OR) 1.67 [(95% CI 1.06–2.64); p = 0.03]} and patients with high FIB-4 index had higher odds of mortality compared to intermediate and low category with an OR 2.22 (95% CI 1.20–4.12; p = 0.01). However, when we evaluated components of FIB-4 (age and AST/ALT ratio), we found that age alone was the best predictor of hospitalization and mortality. Conclusions Among patients at risk of NAFLD with COVID-19 infection, elevated pre-infection FIB-4 index was associated with worsened clinical outcomes, but age was the strongest predictor. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-07120-0.

Liver Fibrosis Scores and Hospitalization, Mechanical Ventilation, Severity, and Death in Patients with COVID-19: A Systematic Review and Dose-Response Meta-Analysis

“…We excluded 421 duplicated records and 285 articles, which were not relevant to the study objective after reviewing the title and abstract. Sixteen articles [ 15 , 16 , 18 , 19 , 29 – 40 ] were finally included after excluding 15 reports for the following reasons: (1) reports that did not report the relevant clinical outcomes or target population ( N = 8), (2) elucidations that were case reports or consisted only of comments ( N = 5), and (3) studies that reported results with an unadjusted estimate effect ( N = 2). The detailed exclusion criteria for each study are described in Supplementary Table S3 .…”

“…Five studies were from Europe, and six publications were from Asia. Ten [ 15 , 16 , 18 , 29 , 31 – 34 , 36 , 38 ] articles reported FIB-4, three [ 30 , 35 , 40 ] reported aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, one [ 39 ] reported NFS, one reported FIB-4 and NFS [ 37 ], and one [ 19 ] assessed FIB-4 and Forns index score. All studies were found to be acceptable ( N ≥ 6) elucidations assessed by the NOS (see Supplementary Table S4 ).…”

“…Ji et al reported that the NAFLD has been reported in up to 38% of patients with COVID-19, and it has been associated with a worse prognosis [ 13 , 14 ]. Moreover, the liver fibrosis score that assesses the advanced fibrosis (e.g., FIB-4 and NFS) was also correlated with increased risk for mechanical ventilation (MV), intensive care, and mortality [ 15 , 16 ]; however, with inconsistent results [ 17 – 19 ]. Furthermore, we noted that the liver fibrosis scores and clinical outcomes in patients with COVID-19 were not comprehensively assessed.…”

COVID-19-associated liver injury: Clinical characteristics, pathophysiological mechanisms and treatment management

“…In general, the prognosis of MALFD patients is determined by the severity of liver fibrosis, not by the presence of steatosis or steatohepatitis, even after the patient is infected with SARS-CoV-2 [84] , [85] . In NAFLD patients with COVID-19, an increase in the Fibrosis-4 (FIB-4) index preinfection was associated with worse clinical outcomes, and age was the strongest predictor of hospitalization and mortality [86] . Compared to patients without or with a low FIB-4 score, MAFLD patients with intermediate or high FIB-4 scores are more likely to be obese, elderly, have diabetes and have higher CRP levels, liver enzyme levels, and NAFLD fibrosis scores and lower platelet and lymphocyte counts, triglyceride levels and high-density lipoprotein cholesterol levels [87] .…”

Liver fibrosis indices predict length of hospitalization and mortality in SARS-CoV-2 infected patients

“…To the best of our knowledge, only few studies had proposed liver brosis non-invasive scores, assessed prior to acute COVID-19 illness, to the risk of more severe disease [15], increased odds of hospitalization [23], and orotracheal intubation [19].…”