We are grateful to Professor Sohn for his comprehensive critique of our paper [1]. As mentioned, the nomenclature for steatotic liver disease has recently changed from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunctionassociated steatotic liver disease (MASLD) [2], and recent publications have adopted this new nomenclature [3,4]. We would like to address two points regarding the use of noninvasive tests (NITs) in patients with MASLD.

First, it is important for both primary and secondary (or higher-level) hospitals to use NITs suited to their specific settings and management purposes. In primary care, targeted screenings are recommended for populations at higher risk of advanced liver disease, including patients with type 2 diabetes mellitus, obesity with metabolic complications, a family history of cirrhosis, or significant alcohol consumption, and these screenings help to identify and rule out advanced liver fibrosis [5]. Patients with hepatic steatosis at higher risk of advanced liver fibrosis should undergo primary risk assessment using the fibrosis-4 (FIB-4) index. If the FIB-4 is <1.3, the patient is at low risk for advanced liver fibrosis and may undergo periodic FIB-4 testing every 1 to 3 years, depending on their cardiometabolic risk factors. Patients at moderate or high risk, based on the FIB-4, should receive secondary risk assessment with vibration-controlled transient elastography (VCTE), which can be performed in either primary or secondary hospitals. The FIB-4 and VCTE are used in different settings and applied sequentially. According to our research, a VCTE cutoff of >7.1 to 7.9 kPa can be used to refer patients to tertiary hospitals for more accurate diagnosis of advanced liver fibrosis [6]. In tertiary hospitals or hepatology centers, the goal is to identify and manage patients with significant liver fibrosis, advanced liver fibrosis, or cirrhosis. Magnetic resonance elastography (MRE), while expensive, is an accurate tool for diagnosing different stages of fibrosis, with a suggested cutoff of >3.62 to 3.8 kPa for diagnosing advanced liver fibrosis.

Second, we should also focus on identifying patients at risk for metabolic dysfunction-associated steatohepatitis (MASH) (F2 or higher). Professor Sohn discussed the use of resmetirom, a promising drug for MASH treatment. In a phase 3 trial, resmetirom resolved non-alcoholic steatohepatitis without worsening of fibrosis in 25.9% of patients in the 80-mg group and 29.9% of patients in the 100-mg group, compared with only 9.7% of patients in the placebo group. Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was seen in 24.2% of patients in the 80-mg group and 25.9% of those in the 100-mg group, compared with 14.2% of patients in the placebo group [7]. Generally, patients at risk for MASH (F2 or higher) are at increased risk of developing cirrhosis and liver-related complications, and thus, it is important to detect and reverse fibrosis progression in the early stage, starting at F2 [5]. Accordingly, MASH patients with F2 are the primary target population for pharmacological treatment because they are the most likely to benefit from MASLD therapies [8]. However, VCTE has limited diagnostic performance in the early stages (with diagnostic areas under the curve in our study of 0.83 for F1, 0.83 for F2, 0.87 for F3, and 0.94 for F4), whereas MRE shows high diagnostic accuracy even at earlier stages but is expensive and not easily accessible. Although our study focused on VCTE and MRE, diagnosing early-stage fibrosis using novel NITs will help identify the target population for MASLD drug therapies.

In summary, NITs should be used according to the medical setting and management goals, and the development of NITs for accurately diagnosing early-stage MASLD is eagerly anticipated.