Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and 1H-MR spectroscopy

Abstract

Introduction: Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP) correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a head-to-head comparison between both methods.

Methods: Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2 34-66%, S3 ≥67%.

Results: Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiver-operating characteristics curves were 0.93 vs. 0.88 for steatosis ≥S1 and 0.94 vs. 0.88 for ≥S2, respectively. Boot-strapping analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2-4 fibrosis TE had sensitivity and specificity of 100% and 98.1% at a cut-off value of 8.85 kPa.

Conclusion: Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification. Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects, anthropometry, and presence of advanced liver fibrosis.

Figure 1. CAP (A) and ¹H-MRS (B) correlate with hepatic steatosis.

CAP and ¹H-MRS values correlate with the amount of hepatic fat and show a stepwise increase compared to the NAS staging (61 and 62 valid measurements available, respectively).

Figure 2. Correlation of CAP and ¹H-MRS.

CAP and ¹H-MRS achieved only a modest correlation, especially in patients with concomitant fibrosis (labeled with squares). A total of 61 valid measurements were available.

Figure 3. CAP and TE cut-off values for clinical use.

Application of published cut-off values for TE (7.9 kPa) and CAP (252 dB/m²) results in high sensitivity for detection of distinct fibrosis and steatosis (A) , . CAP values between 215 dB/m and 300 dB/m require further diagnostic procedures for differentiation of the degree of steatosis (“grey area”) (B).

Figure 4. Positive and negative predictive values as well as proportion of uncharacterized cases as they depend upon prevalence.

S0–1 patients and controls were classified as healthy and S2–3 as sick. The diagnostic procedure made use of CAP where those with values below 215 dB/m were diagnosed as healthy, those with values above 300 dB/m (or 252 dB/m, dashed lines) were diagnosed as sick and those in between were not diagnosed. A total of 61 valid measurements were available.