Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Abstract

Markers are needed to predict progression of nonalcoholic fatty liver disease (NAFLD). The proton density fat fraction, measured by magnetic resonance imaging (MRI-PDFF), provides an accurate, validated marker of hepatic steatosis; however, it is not clear whether the PDFF identifies patients at risk for NAFLD progression. We performed a follow-up study of 95 well-characterized patients with biopsy-proven NAFLD and examined the association between liver fat content and fibrosis progression. MRI-PDFF measurements were made at study entry (baseline). Biopsies were collected from patients at baseline and after a mean time period of 1.75 years. Among patients with no fibrosis at baseline, a higher proportion of patients in the higher liver fat group (MRI-PDFF ≥15.7%) had fibrosis progression (38.1%) than in the lower liver fat group (11.8%) (P = .067). In multivariable-adjusted logistic regression models (adjusted for age, sex, ethnicity, and body mass index), patients in the higher liver fat group had a significantly higher risk of fibrosis progression (multivariable-adjusted odds ratio 6.7; 95% confidence interval 1.01-44.1; P = .049). Our findings associate higher liver fat content, measured by MRI-PDFF, with fibrosis progression.

Hepatic fat as clinical outcome and therapeutic target for nonalcoholic fatty liver disease

“…MRI‐PDFF measurement correlates with histologically determined steatosis both in cross‐sectional and in prospective evaluation . In keeping with a causal role of hepatic fat in determining liver disease progression, high MRI‐PDFF has now been associated with liver fibrosis progression, independently of several metabolic confounders . This evidence makes evaluation of MRI‐PDFF an attractive option for non‐invasive yet accurate quantification of hepatic fat content in early‐stage NAFLD trials evaluating treatments that modulate fat accumulation .…”

“…16,17 On the other hand, accurately quantified hepatic fat has now been linked with liver fibrosis progression. 18,19 Although fibrogenesis may self-perpetuate independently of hepatic fat and inflammation after a wound healing response has been initiated, in patients with NAFLD without advanced disease amelioration of the metabolic profile and hepatic fat as a consequence of lifestyle modifications or bariatric surgery has been associated with resolution of NASH and improvement in fibrosis in those with more marked weight loss. 20,21 Therefore, evaluation of fibrosis associated with hepatic fat accumulation ("steatofibrosis") may represent a simpler marker of disease evolution in clinical practice and therapeutic trials.…”

“…40 In keeping with a causal role of hepatic fat in determining liver disease progression, high MRI-PDFF has now been associated with liver fibrosis progression, independently of several metabolic confounders. 18 This evidence makes evaluation of MRI-PDFF an attractive option for non-invasive yet accurate quantification of hepatic fat content in early-stage NAFLD trials evaluating treatments that modulate fat accumulation. 41 However, although this approach is less invasive and resource consuming than liver biopsy, it would be impractical and still too expensive to be implemented in routine clinical practice and for screening purposes.…”

Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease

“…This was a cross-sectional analysis of a discovery cohort that included 156 participants prospectively recruited between October 2011 and May 2014 at the University of California at San Diego (UCSD) NAFLD Research Center. [22][23][24][25] All patients with suspected NAFLD with a clinical indication for liver biopsy underwent a careful evaluation for other causes of hepatic steatosis and liver disease through a standardised research visit including detailed medical and alcohol use history as well as anthropometric and physical examination. The study was performed according to STARD criteria listed in online supplementary table 1.…”

Editorial: role of leucine‐metformin‐sildenafil combination in the treatment of nonalcoholic fatty liver disease (NAFLD)

“…It included patients with MRIPDFF ≥15% which would have allowed us to see a significant difference relative to placebo thereby reducing the likelihood of type 2 error. Indeed, it was recently shown that patients with higher liver fat (MRIPDFF ≥15.7%) have higher fibrosis progression . Thus, these trial participants were more likely to have progressive NAFLD and were appropriate candidates for an early phase trial.…”