Liver Fibrosis Scores and Hospitalization, Mechanical Ventilation, Severity, and Death in Patients with COVID-19: A Systematic Review and Dose-Response Meta-Analysis
Menglu Liu, Kaibo Mei, Ziqi Tan, Shan Huang, Fuwei Liu, Chao Deng, Jianyong Ma, Peng Yu, Xiao Liu
Abstract
Background and Aim. The relationship between liver fibrosis scores and clinical outcomes in patients with COVID-19 is not compressively assessed. Methods. We identified relevant cohort studies that assessed the relationship between liver fibrosis scores (e.g., FIB-4, NAFLD fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)) and associated prognosis outcomes by searching the PubMed, EMBASE, and medRxiv databases. The potential dose-response effect was performed using a stage robust error meta-regression. Results. Sixteen studies with 8,736 hospitalized patients with COVID-19 were included. One-point score in FIB-4 increase was significantly associated with increased mechanical ventilation (RR: 2.23, 95% CI: 1.37–3.65, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>P</a:mi> <a:mo>=</a:mo> <a:mn>0.001</a:mn> </a:math> ), severe COVID-19 (RR: 1.82, 95% CI: 1.53–2.16, <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo><</c:mo> <c:mn>0.001</c:mn> </c:math> ), and death (RR: 1.47, 95% CI: 1.31–1.65, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo><</e:mo> <e:mn>0.001</e:mn> </e:math> ), rather than hospitalization (RR: 1.35, 95% CI: 0.72–2.56, <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.35</g:mn> </g:math> ). Furthermore, there is a significant positive linear relationship between FIB-4 and severe COVID-19 ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:msub> <i:mrow> <i:mi>P</i:mi> </i:mrow> <i:mrow> <i:mtext>nonlinearity</i:mtext> </i:mrow> </i:msub> <i:mo>=</i:mo> <i:mn>0.12</i:mn> </i:math> ) and mortality ( <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:msub> <k:mrow> <k:mi>P</k:mi> </k:mrow> <k:mrow> <k:mtext>nonlinearity</k:mtext> </k:mrow> </k:msub> <k:mo>=</k:mo> <k:mn>0.18</k:mn> </k:math> ). Regarding other liver scores, one unit elevation in APRI increased the risk of death by 178% (RR: 2.78, 95% CI: 1.10–6.99, <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>P</m:mi> <m:mo>=</m:mo> <m:mn>0.03</m:mn> </m:math> ). Higher NFS (≥−1.5) and Forns index were associated with increased risk of severe COVID-19 and COVID-19-associated death. Conclusion. Our dose-response meta-analysis suggests high liver fibrosis scores are associated with worse prognosis in patients with COVID-19. For patients with COVID-19 at admission, especially for those with coexisting chronic liver diseases, assessment of liver fibrosis scores might be useful for identifying high risk of developing severe COVID-19 cases and worse outcomes.