Longitudinal Prognostic Value of the Most Common Algorithms for Fibrosis in Non-Alcoholic Fatty Liver Disease. An International Study in Non-Cirrhotic, Biopsy-Proven Patients.
R.Younes, C.Rosso, M.Garcia, S.Petta, L.Miele, A.Liguori, P.Francione, A.Fracanzani, L.Valenti, QM Anstee, E.Bugianesi
Background and aims:Non-alcoholic fatty liver disease (NAFLD) is a global health concern since it may progress to Steatohepatitis (NASH) and ultimately cirrhosis. As fibrosis is the main determinant of progressive disease, an important unmet need is to establish a defined set of biomarkers that enable detection of fibrotic NASH and can predict liver-related morbidity and mortality. We aimed at validating the long-term prognostic value of the most currently used non-invasive fibrosis scores in a cohort of biopsy-proven NAFLD patients.
Methods:918 prospectively recruited patients underwent a liver biopsy for clinical suspicion of NAFLD in main referral tertiary centres in Italy (Turin, Milan, Rome, Palermo) and the United Kingdom (Newcastle). Clinical and biochemical data were collected at the time of biopsy and throughout the follow up. The following non-invasive fibrosis scores were calculated: NAFLD Fibrosis Score (NFS), APRI, FIB-4, BAAT and BARD
Results:At baseline, 593 patients (65%) presented non-alcoholic steatohepatitis (NASH) and 220 (24%) had moderate or advanced fibrosis. After a median follow up of 85 months (9-336), 75 patients developed liver-related events (ascites, oesophageal varices or hepatic encephalopathy), 15 patients developed hepatocellular carcinoma (HCC) while 91 patients presented cardiovascular events. Among the non-invasive scores, NFS and FIB4 had the highest potential to predict both liver events and HCC (AUROC Liver Events 0,76 for both NFS and FIB4; AUROC HCC 0,82 and 0,80 for NFS and FIB4 respectively). Despite all the scores did not show a high impact on the prediction of the cardiologic outcome, patients with a BAAT of 4 or a BARD score ≥ 2 presented a higher risk of developing cardiovascular events (OR 8,82 and 2,175 respectively). The survival analysis demonstrated that patients who presented a NFS > 0,675, a FIB4 > 2,67, an APRI > 1 or a BARD score ≥ 2 reported a worse survival outcome (Log Rank < 0,001 for NFS, FIB4 and APRI; 0,006 for BARD). No additional value was obtained when the different scores were combined together.
Conclusions:The lack of a prognostic biomarker for NAFLD and the ability of these algorithms to predict long-term NAFLD outcomes suggest the use of these scores in routine clinical practice may represent a tool to stratify patients at risk and to select patients for targeted therapies or pharmaceutical trials.
Funded by Horizon2020 under grant agreement 634413, EPoS; grant agreement 777377, LITMUS Figure 1
