Prognostic accuracy of FIB‐4, NAFLD fibrosis score and APRI for NAFLD‐related events: A systematic review

Abstract

Background & Aims Fibrosis is the strongest predictor for long‐term clinical outcomes among patients with non‐alcoholic fatty liver disease (NAFLD). There is growing interest in employing non‐invasive methods for risk stratification based on prognosis. FIB‐4, NFS and APRI are models commonly used for detecting fibrosis among NAFLD patients. We aimed to synthesize existing literature on the ability of these models in prognosticating NAFLD‐related events. Methods A sensitive search was conducted in two medical databases to retrieve studies evaluating the prognostic accuracy of FIB‐4, NFS and APRI among NAFLD patients. Target events were change in fibrosis, liver‐related event and mortality. Two reviewers independently performed reference screening, data extraction and quality assessment (QUAPAS tool). Results A total of 13 studies (FIB‐4:12, NFS: 11, APRI: 10), published between 2013 and 2019, were retrieved. All studies were conducted in a secondary or tertiary care setting, with follow‐up ranging from 1 to 20 years. All three markers showed consistently good prognostication of liver‐related events (AUC from 0.69 to 0.92). For mortality, FIB‐4 (AUC of 0.67‐0.82) and NFS (AUC of 0.70‐0.83) outperformed APRI (AUC of 0.52‐0.73) in all studies. All markers had inconsistent performance for predicting change in fibrosis stage. Conclusions FIB‐4, NFS, and APRI have demonstrated ability to risk stratify patients for liver‐related morbidity and mortality, with comparable performance to a liver biopsy, although more head‐to‐head studies are needed to validate this. More refined models to prognosticate NAFLD‐events may further enhance performance and clinical utility of non‐invasive markers.

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

“…D-Assessment of disease determinants in individual patients is not routinely performed in clinical practice nor in RCTs despite the fact that a variety of pathogenic risk factors are well characterized. In our view, all the following features are important modifiers that are worth registering in the individual patient and should be taken into consideration in therapeutic [193,194] AST, platelets studies: (i) sex and reproductive status, (ii) genetics, (iii) intestinal microbiota, (iv) endocrine assessment, (v) metabolic assessment, and (vi) physical activity. Existing data on the role of these factors in NAFLD are summarized in ''Sex, Gender, and Reproductive Status''.…”

Effects of Tamoxifen vs. Toremifene on fatty liver development and lipid profiles in breast Cancer

“…It has been reported that advanced fibrosis is a crucial prognostic factor for NAFLD. Several studies have revealed that APRI and FIB-4 can stratify the risks of liverrelated morbidity and mortality [29]. This study found that liver fibrosis scores showed statistically significant differences between the TAM and TOR groups, independent of obesity and diabetes.…”

European ‘NAFLD Preparedness Index’ — Is Europe ready to meet the challenge of fatty liver disease?

“…Prediction rules based on a combination of serological biomarkers, such as FIB-4, are slowly paving the way to more acceptable and affordable indicators for the identification of patients at high-risk of progressive disease, which could be successfully used in primary care for diagnosis and adequate referral to specialised services. 52,53 Unfortunately, patients with NAFLD, including those with NASH associated advanced fibrosis or cirrhosis, often remain undetected until an incidental diagnosis or decompensation of liver cirrhosis, which contributes to increasing trends in NAFLD-related morbidity and mortality. This ineffective "filter" at the primary care level due in part to inadequate knowledge of non-invasive surrogate J o u r n a l P r e -p r o o f markers of fibrosis 54 could be improved by the use of defined care pathways which utilise a NAFLDspecific stepwise algorithm to guide clinical decisions and to improve referral to specialised services.…”