## 2 AI Applications and Research in NAFLD
### Liver Fibrosis  
A variable percentage of patients with NAFLD develop NASH, which furthermore leads to fibrotic changes. Sustained and progressive fibrosis is a long-term process, but patients can present with end-stage liver disease and fibrosis, which is also the most significant predictor of prognosis in NAFLD. In a systematic review and meta-analysis, [PERSON] et al. found that the risk for all-cause and liver-related mortality increases as the fibrosis progresses to higher stages in patients with NAFLD [23]. Thus, accurate non-invasive fibrosis tests play a significant role in lowering the increasing incidence of liver cirrhosis and hepatocellular carcinoma. The degree of liver fibrosis is also important in the evaluation of NAFLD patients, with non-invasive methods such as real-time elastography (RTE) or shear-wave elastography (SWE) being extensively used instead of liver biopsies [24]. RTE was proposed initially for the evaluation of liver fibrosis in chronic hepatitis with a good correlation between the elasticity scores obtained using RTE and the histological fibrosis stage [25]. A direct comparison between RTE and transient elastography (Fibroscan)showed the superiority of RTE for the diagnosis of liver fibrosis in chronic hepatitis C [26]. The method was validated in both chronic hepatitis B and C [27; 28]. RTE has been used in patients with NAFLD, with a diagnostic accuracy of 82.6-96.0% based on cut-offs of 2.47 for F1, 2.67 for F2, 3.02 for F3 and 3.36 for F4 [29]. Additionally, the Liver Fibrosis Index was calculated based on RTE and showed a significant correlation with the increasing histological severity of fibrosis in both chronic hepatitis C and NAFLD [30]. These data were confirmed in a meta-analysis that compared transient elastography, acoustic radiation force impulse (ARFI) imaging and RTE, indicating a similar overall accuracy for the evaluation of significant liver fibrosis [31]. Real-time SWE is also considered accurate for the evaluation of liver fibrosis in chronic hepatitis C, more accurate than transient elastography for the assessment of significant liver fibrosis [32]. A recent meta-analysis showed that pSWE and transient elastography have similar accuracies in the detection of significant fibrosis, advanced fibrosis and cirrhosis in patients with NAFLD [33]. Even though both methods have limitations for obese patients, 2D SWE was shown to be feasible in severely obese patients, as it was successfully performed in 97.3% of patients and was correlated with BMI, waist circumference, NAFLD activity score and steatosis in a univariate analysis [34]. Furthermore, transient elastography, 2D SWE and MRI have similar diagnostic accuracies for significant and especially for advanced fibrosis in patients with biopsy-proven NAFLD [35]. Multiparametric ultrasound techniques including dispersion slope ((m/s)/kHz), attenuation coefficient (dB/cm/MHz) and shear-wave speed (in meters per second) allow the discrimination of inflammation (A1 to A3), steatosis (S1 to S3) and fibrosis (F1 to F4: cirrhosis), with the combination yielding an area under the receiver operating curve of 0.81% for patients with biopsy-proven NAFLD [36]. The introduction of attenuation imaging represented a significant step forward in ultrasound technologies in order to accurately quantify liver fibrosis and steatosis in NAFLD patients [37]. The accuracy of various techniques of elastography (vibration controlled transient elastography, pSWE and 2D SWE) in comparison with MRI in NAFLD patients was analysed in a recent meta-analysis, showing acceptable summary estimates of the area under the receiver operating curve for the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis [38].