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Ballestri et al. Metab Target Organ Damage 2023;3:1 Metabolism and
DOI: 10.20517/mtod.2022.23
Target Organ Damage

Review Open Access

Liver fibrosis in nonalcoholic fatty liver disease
patients: noninvasive evaluation and correlation

with cardiovascular disease and mortality

1,#
1
2,#
1
3
Stefano Ballestri , Alessandro Mantovani , Maria Di Girolamo , Enrica Baldelli , Mariano Capitelli ,
Amedeo Lonardo 4
1
Internal Medicine Unit, Hospital of Pavullo, Azienda USL of Modena, Modena 41026, Italy.
2
Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona,
Verona 37126, Italy.
3
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41126, Italy.
4
Department of Internal Medicine. Operating Unit of Internal Medicine, Ospedale Civile di Baggiovara, Azienda Ospedaliero-
Universitaria of Modena, Modena 41126, Italy.
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Authors contributed equally.
Correspondence to: M.D. Stefano Ballestri, Internal Medicine Unit, Hospital of Pavullo, Azienda USL of Modena, Via Suore di S.
Giuseppe Benedetto Cottolengo 5, Pavullo nel Frignano, Modena 41026, Italy. E-mail: s.ballestri@ausl.mo.it
How to cite this article: Ballestri S, Mantovani A, Di Girolamo M, Baldelli E, Capitelli M, Lonardo A. Liver fibrosis in nonalcoholic
fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality. Metab Target Organ
Damage 2023;3:1. https://dx.doi.org/10.20517/mtod.2022.23
Received: 30 Jul 2022 Revised: 27 Sep 2022 Accepted: 9 Jan 2023 Published: 31 Jan 2023

Academic Editors: Youngmi Jung, Laura E. Nagy, María Luz Martínez-Chantar Copy Editor: Ke-Cui Yang Production Editor:
Ke-Cui Yang

Abstract
Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology,
including nonalcoholic fatty liver disease (NAFLD). NAFLD has been viewed as an independent correlate of
cardiovascular risk. This review article briefly describes the cellular and molecular pathomechanisms underlying
hepatic fibrosis. We then address noninvasive assessment of liver fibrosis. Finally, we discuss published evidence
supporting fibrosis biomarkers’ role in assessing cardiovascular risk among patients with NAFLD. While
histological assessment is the diagnostic standard of hepatic fibrosis, we specifically address noninvasive
techniques, including equations based on anthropometric parameters, laboratory indices, and elastometry obtained
with imaging techniques. The former group includes AST: ALT ratio, the Forns Index, the AST-to-platelet ratio
index score, BARD (BMI, AAR, Diabetes) score, the fibrosis-4 index (FIB-4), the NAFLD fibrosis score, the gamma-
glutamyl transferase-to-platelet ratio, and the Hepamet fibrosis score. The latter comprises elastographic

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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