Abstract
The prevalence and severity of non-alcoholic fatty liver disease (NAFLD) is increasing, yet adequately validated tests for care paths are limited and non-invasive markers of disease progression are urgently needed. The aim of this work was to summarize the performance of Pro-C3, a biomarker of active fibrogenesis, in detecting significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), cirrhosis (F4) and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. A sensitive search of five databases was performed in July 2021. Studies reporting Pro-C3 measurements and liver histology in adults with NAFLD without co-existing liver diseases were eligible. Meta-analysis was conducted by applying a bivariate random effects model to produce summary estimates of Pro-C3 accuracy. From 35 evaluated reports, eight studies met our inclusion criteria; 1568 patients were included in our meta-analysis of significant fibrosis and 2058 in that of advanced fibrosis. The area under the summary curve was 0.81 (95% CI 0.77–0.84) in detecting significant fibrosis and 0.79 (95% CI 0.73–0.82) for advanced fibrosis. Our results support Pro-C3 as an important candidate biomarker for non-invasive assessment of liver fibrosis in NAFLD. Further direct comparisons with currently recommended non-invasive tests will demonstrate whether Pro-C3 panels can outperform these tests, and improve care paths for patients with NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic liver disease that is estimated to affect around 25% of the worldwide population [1]
From the 35 records on Pro-C3 which were identified in the search, eight studies were eligible for inclusion in the systematic review
We summarized the evidence on the accuracy of Pro-C3 in detecting target conditions within the non-alcoholic fatty liver disease (NAFLD) spectrum: significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), or non-alcoholic steatohepatitis (NASH)
Summary
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic liver disease that is estimated to affect around 25% of the worldwide population [1]. Biomedicines 2021, 9, 1920 mellitus (T2DM) [1]. Most individuals with NAFLD are in the first stage of simple steatosis without clinical symptoms, a considerable portion will progress into nonalcoholic steatohepatitis (NASH) and/or hepatic fibrosis, which may lead to cirrhosis and liver-related mortality [2,3]. Liver fibrosis is the main predictor of mortality in patients with NAFLD [4,5]. A key question in the field is to identify patients with advanced liver fibrosis in order to ensure preventative measures before irreversible liver damage occurs. Patients in advanced and potentially active and progressive stages of NAFLD are the ones most likely to benefit from anti-NASH drugs that are currently being developed [6]
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