Assessing the severity of liver fibrosis and steatosis in biopsy-proven NAFLD patients using MR imaging, transient elastography and serum biomarker

Abstract

Background: Because nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease, a non-invasive diagnosis of the disease severity is urgently needed. To diagnose liver fibrosis, transient elastography (TE) has an acceptable accuracy in viral related liver disease. However, in patients with severe steatosis, TE falls short in terms of the accuracy. The aim of our study is to analyze hepatic fibrosis, steatosis, and inflammation in patients with biopsy-proven NAFLD using MR imaging, TE, and serum biomarkers. We plan to enroll one hundred patients until 2018. This is a preliminary report of our study.

Methods: This is a multicenter prospective study of patients with biopsy-proven NAFLD. The patients underwent liver biopsy, MRI and TE 6 months before enrollment. Sera were collected at the time of enrollment. MRI examination included mDIXON, MR spectroscopy (MRS), and MR elastography (MRE). TE measured liver stiffness and controlled attenuation parameter (CAP). Twenty serum biomarkers were analyzed with the Luminex Multiplex Assay.

Results: Thirty-five patients with biopsy-proven NAFLD were enrolled from October 2016 to March 2017. Mean age and BMI were 50.6 ± 0.48 years and 28.50 ±4.87 kg/m2, respectively. Female patients were dominant (23, 65.7%), and other co-morbidities were diabetes (n=15, 42.9%), hypertension (n=12, 34.3%) and dyslipidemia (n=11, 31.4%). For the diagnosis of advanced fibrosis (stage 3-4), the AUROC of the MRE tended to be superior (0.89; 95%CI, 0.72-0.98) compared with the TE (0.83; 95%CI, 0.66-0.93) (P=0.40). For the diagnosis of severe steatosis (stage 2-3), CAP (0.7; 95%CI, 0.52-0.84) had a lower AUROC compared with the mDIXON (0.83; 95% CI, 0.65-0.94; P=0.11) and MRS (0.82; 95%CI, 0.63-0.93; P=0.28), respectively. In the serum biomarker analysis, increased resistin had a significant association with severe steatosis (stage 2-3) compared to mild steatosis (stage 0-1) (OR=1.44; 95%CI, 1.01-2.06; P=0.04). Increased IFN-gamma was associated with severe inflammation (stage 2-3) compared to mild inflammation (stage 0-1) (OR=1.36; 95%CI, 1.01-1.83; P=0.04). Total PAI-1 showed a tendency for association with the presence of NASH (OR=1.063; 95%CI, 0.99-1.14; P=0.07).

Conclusion: In our preliminary results, MRI (mDIXON, MRS and MRE) tended to identify more severe steatosis and fibrosis compared to TE in patients with biopsy-proven NAFLD. Serum IFN-gamma was significantly associated with inflammation, and serum resistin was also associated with steatosis. Non-invasive modalities using MRI and serum biomarkers could be potential tools for the diagnosis and classification of disease severity in patients with NAFLD.