Non-invasive tests for advanced fibrosis in patients with NAFLD

09 Sep 2021

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition that contains within its definition numerous possible different clinical forms. At present time, however, definition criteria are based on the findings of the histological investigation of a liver biopsy [Ref 1]. In particular, the main findings for the diagnosis are the presence of steatosis, ballooning and lobular inflammation. Many other histological features such portal inflammation, polymorphonucleate infiltrates, Mallory-Denk bodies, apoptotic bodies, clear vacuolated nuclei, microvacuolar steatosis can be observed in liver biopsies of patients with NAFLD, but they’re not necessary for the diagnosis [Ref 2]. Diagnosis based on liver biopsy can however be tricky, since its accuracy can be limited by sampling variability and observer-related discrepancies. Moreover, liver biopsy is an invasive procedure that has its own risk of complications, mainly major or minor bleeding [Ref 3]. Over the years, many non-invasive tools have been developed for the diagnosis of liver fibrosis. Although not officially recognized for the diagnosis of NAFLD, some of these tests seem to have a quite high diagnostic accuracy in these patients.

Apart from liver stiffness measured with transient elastography, many predictive scores based only on clinical data have been evaluated through the years.

NAFLD Fibrosis Score (NSF) is a score that is based only on anamnestic and biochemical data such as age, Body Mass Index (BMI), the presence of impaired fasting glucose or diabetes, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, platelet count and albumin. Fibrosis is probable for values <-1.455, while it is unlikely when values are >0.676 [Ref 4].

Fibrosis-4 (FIB-4) is a score that was initially designed to evaluate fibrosis in patients with HCV/HIV coinfection, and is based on the values of age, AST, ALT and platelet count [Ref 5].

AST to ALT ratio is based on the value of the transaminases value and correlates positively with the stage of fibrosis in patients with HCV infection. [Ref 6].

Also AST-to-platelet ratio index (APRI) was created to assess the stage of fibrosis in patients with HCV infection and is based only on biochemical values. It demonstrated a good degree of accuracy in predicting the stage of fibrosis in patients with viral cirrhosis [Ref 7].

In a recent meta-analysis, FIB-4 and NFS showed AUROCs of 0.76 and 0.73 for identifying F3 fibrosis and AUROCs of 0.80 and 0.78 respectively for identifying cirrhosis in patients with NAFLD [Ref 8]. These values are lower than those of liver stiffness measured with transient elastography, that showed an AUROC of 0.85 for identifying F3 fibrosis and 0.90 for identifying cirrhosis. These data were extrapolated from studies with a small population, and it is difficult to give the correct scientific weight to these findings. However, they can be seen as promising, especially considering the possibility to integrate the use of clinical scores with liver stiffness measurements. It is therefore clear that there is a need to review these data in a larger population.


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  8. Mózes FE, Lee JA, Selvaraj EA, et al. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut. 2021 May 17:gutjnl-2021-324243. Epub ahead of print.