From NAFLD to NASH: Determining Disease Progression and Regression Rates

The spectrum of non-alcoholic fatty liver disease (NAFLD) is divisible into three stages: 1) NAFL, 2) non-alcoholic steatohepatitis (NASH), NAFLD’s progressive and inflammatory subtype, and 3) NAFLD or NASH with fibrosis, whose stages range from F0-4.
PUBLISHED IN: Clinical Gastroenterology and Hepatology (May 2023)


It is well-known that patients with NASH and significant fibrosis (≥F2) are at a higher risk of liver-related events. Despite this, NAFL’s natural progression to NASH remains inadequately explored. Even fewer studies address the possibility of both conditions’ regression.

This article aimed to explore findings from Le et al. (2022)’s systematic review and meta-analysis of paired biopsy or imaging studies, in which disease state transition probabilities across the NAFL spectrum were defined.

Key learnings:

Compared to previous systematic reviews and meta-analyses, Le et al. (2022)’s study exhibits a higher granularity and precision, as it addresses the entire NAFL spectrum, ranging from normal liver to the highest fibrosis stage (F4). It also informs on liver disease progression and regression rates: indeed, progression to NASH was found to be more common than regression from it. Moreover, compared to those with mild fibrosis, patients with advanced fibrosis demonstrated an increased likelihood of regression. Despite the quality of this study, its estimations of progression and regression rates are limited by the inherent flaws in the research it analyses. Selection bias, for instance, is notable in liver biopsy studies from randomised clinical trials and longitudinal cohorts. Sampling, intraobserver, and interobserver variability of paired liver biopsy assessments further plague many studies with longer follow-ups. Moreover, follow-up liver biopsies conducted by observational studies are often performed at irregular intervals. The serial use of inadequately evaluated noninvasive tests for patient monitoring limits also such studies’ findings. These limitations ultimately create uncertainty around Le et al.’s original projections. High-quality studies on disease progression and regression in both untreated and treated patients which address such methodological flaws are thus needed to improve estimations of disease progression and regression rates.

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S Duarte, BSc

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