Abstract

BackgroundReliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined.MethodsWe retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors.ResultsA score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%.ConclusionsOur results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients.

Highlights

  • Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined

  • Akuta et al BMC Gastroenterology (2021) 21:434 to non-alcoholic steatohepatitis (NASH), which may progress to liver cirrhosis, liver cancer, and to liver failure [7]

  • The areas under the area under the receiver operating characteristic (AUROC) of the FIB-4 index for detection of stages ≥ 1, ≥ 2, ≥ 3, and 4 were 0.75, 0.84, 0.85, and 0.90, respectively

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Summary

Introduction

Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined. The most common worldwide liver disease is non-alcoholic fatty liver disease (NAFLD) [1,2,3,4,5,6]. The American Association for the Study of Liver Diseases reported that the most common cause of death in patients with NAFLD is related to cardiovascular diseases (CVDs) independent of other metabolic comorbidities. In Asia, the incidence rates of CVDs, malignancies, and liver-related events in patients with histo-pathologically confirmed NAFLD still remains unclear. The stage of fibrosis, exclusive of other histopathological features of steatohepatitis, has been reported to be an independent and significant predictor of overall mortality, need for liver transplantation, and liver-related events [10]. Reliable, non-histological, and noninvasive predictors of the top three causes of death have not yet been found

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