Multicenter Validation of Association Between Decline in... : Hepatology (original) (raw)

Original Articles: Steatohepatitis/Metabolic Liver Disease

Multicenter Validation of Association Between Decline in MRI‐PDFF and Histologic Response in NASH

Loomba, Rohit*,1; Neuschwander‐Tetri, Brent A2; Sanyal, Arun3; Chalasani, Naga4; Diehl, Anna Mae5; Terrault, Norah6; Kowdley, Kris7; Dasarathy, Srinivasan8; Kleiner, David9; Behling, Cynthia1; Lavine, Joel10; Van Natta, Mark11; Middleton, Michael1; Tonascia, James11; Sirlin, Claude1; for the NASH Clinical Research Network

1NAFLD Research Center, Division of Gastroenterology and Hepatology Department of MedicineUniversity of California San DiegoLa JollaCA

2Division of Gastroenterology and Hepatology, Department of MedicineSaint Louis UniversitySt. LouisMO

3Division of Gastroenterology, Hepatology and Nutrition, Department of MedicineVirginia Commonwealth UniversityRichmondVA

4Division of Gastroenterology, Department of MedicineIndiana UniversityIndianapolisIN

5Division of Gastroenterology and Hepatology, Department of MedicineDuke UniversityDurhamNC

6Division of Gastroenterology, Department of MedicineUniversity of California San FranciscoSan FranciscoCA

7Liver Center, Department of MedicineSwedish Medical CenterSeattleWA

8Division of Gastroenterology, Department of MedicineCleveland ClinicClevelandOH

9Laboratory of PathologyThe National Cancer InstituteBethesdaMD

10Division of Gastroenterology, Department of PediatricsColumbia UniversityNew YorkNY

11Department of Epidemiology, Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreMD

* Address Correspondence and Reprint Requests to:
Rohit Loomba, M.D., M.H.Sc.
University of California at San Diego
Altman Clinical and Translational Research Institute
1W202, 9500 Gilman Drive
La Jolla, CA 92093‐0887
E‐mail: [email protected]
Tel.: +858‐246‐2201

Abstract

Background and Aims

Emerging data from a single‐center study suggests that a 30% relative reduction in liver fat content as assessed by magnetic resonance imaging–proton density fat fraction (MRI‐PDFF) from baseline may be associated with histologic improvement in nonalcoholic steatohepatitis (NASH). There are limited multicenter data comparing an active drug versus placebo on the association between the quantity of liver fat reduction assessed by MRI‐PDFF and histologic response in NASH. This study aims to examine the association between 30% relative reduction in MRI‐PDFF and histologic response in obeticholic acid (OCA) versus placebo‐treated patients in the FLINT (farnesoid X receptor ligand obeticholic acid in NASH trial).

Approach and Results

This is a secondary analysis of the FLINT trial including 78 patients with MRI‐PDFF measured before and after treatment along with paired liver histology assessment. Histologic response was defined as a 2‐point improvement in nonalcoholic fatty liver disease activity score without worsening of fibrosis. OCA (25 mg orally once daily) was better than placebo in improving MRI‐PDFF by an absolute difference of −3.4% (95% confidence interval [CI], −6.5 to −0.2%, P value = 0.04) and relative difference of −17% (95% CI, −34 to 0%, P value = 0.05). The optimal cutoff point for relative decline in MRI‐PDFF for histologic response was 30% (using Youden’s index). The rate of histologic response in those who achieved less than 30% decline in MRI‐PDFF versus those who achieved a 30% or greater decline in MRI‐PDFF (MRI‐PDFF responders) relative to baseline was 19% versus 50%, respectively. Compared with MRI‐PDFF nonresponders, MRI‐PDFF responders demonstrated both a statistically and clinically significant higher odds 4.86 (95% CI, 1.4‐12.8, P value < 0.009) of histologic response, including significant improvements in both steatosis and ballooning.

Conclusion

OCA was better than placebo in reducing liver fat. This multicenter trial provides data regarding the association between 30% decline in MRI‐PDFF relative to baseline and histologic response in NASH.