Clinical Utility of Combined MRI-PDFF and ALT Response in Predicting Histologic Response in Nonalcoholic Fatty Liver Disease.

Nonalcoholic steatohepatitis (NASH) is the inflammatory form of nonalcoholic fatty liver disease (NAFLD) that can progress to cirrhosis and hepatocellular carcinoma. 1 Loomba R. et al. Cell. 2021; 184: 2537-2564 Abstract Full Text Full Text PDF PubMed Scopus (523) Google Scholar , 2 Tan D.J.H. et al. Lancet Oncol. 2022; 23: 521-530 Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar , 3 Huang D.Q. et al. Aliment Pharmacol Ther. 2022; 55: 820-827 Crossref PubMed Scopus (24) Google Scholar , 4 Huang D.Q. et al. Cell Metab. 2022; 34: 969-977.e2 Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Histologic response (a 2-point improvement in the NAFLD Activity Score with at least 1-point improvement in lobular inflammation or ballooning and no worsening of fibrosis) and NASH resolution (defined by the NASH Clinical Research Network as no more than mild residual inflammatory cells [score of 0 or 1] and no hepatocyte ballooning [score of 0] and no worsening of fibrosis) are used to evaluate treatment response in phase 2b clinical trials of patients with NASH. 5 Loomba R. et al. Gastroenterology. 2019; 156: 88-95.e5 Abstract Full Text Full Text PDF PubMed Google Scholar , 6 Kleiner D.E. et al. Hepatology. 2005; 41: 1313-1321 Crossref PubMed Scopus (7701) Google Scholar , 7 Neuschwander-Tetri B.A. et al. Lancet. 2015; 385: 956-965 Abstract Full Text Full Text PDF PubMed Scopus (1670) Google Scholar , 8 Loomba R. et al. Gastroenterology. 2022; 162: 680-688 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Liver biopsy remains the gold standard for determining disease activity but is limited by potential complications and sampling variability. Emerging data suggest that ≥30% decline in magnetic resonance imaging (MRI) proton density fat fraction (PDFF) (defined as MRI-PDFF response) and ≥17-U/L decrease in alanine aminotransferase (ALT) (defined as ALT response) are associated with higher odds of histologic response and NASH resolution. 5 Loomba R. et al. Gastroenterology. 2019; 156: 88-95.e5 Abstract Full Text Full Text PDF PubMed Google Scholar ,9 Stine J.G. et al. Clin Gastroenterol Hepatol. 2021; 19: 2274-2283.e5 Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar ,10 Loomba R. et al. Hepatology. 2020; 72: 1219-1229 Crossref PubMed Scopus (63) Google Scholar However, the association between a combined MRI-PDFF and ALT response with histologic response or resolution of NASH has not been systematically assessed. Utilizing a well-characterized, prospective cohort of patients with NAFLD who had a paired liver biopsy and contemporaneous MRI-PDFF assessment, we examined the association between combined MRI-PDFF and ALT response with histologic response or resolution of NASH on liver biopsy using the NASH Clinical Research Network Histologic Scoring System. We determined that a combined MRI-PDFF and ALT response is associated with higher odds of histologic response or NASH resolution than either MRI-PDFF or ALT response alone, and it appears additive.