We thank Dr Wittmer et al for their interest and thoughtful comments regarding our article “Approach to steatotic liver disease in the office. Diagnosis, management, and proposed nomenclature” in the April 2025 issue of Canadian Family Physician.1 We appreciate the concerns raised by Dr Wittmer and colleagues.

The review of metabolic dysfunction–associated steatotic liver disease (MASLD) was prompted by the ongoing pandemic accompanying obesity and diabetes. Our main objective was to point out that steatotic liver disease (SLD) is a manifestation of accompanying comorbidities related to metabolic disorders. Also, we wanted to familiarize readership with new nomenclature. As a result of its significance, multiple trials and studies have been published with rapid changes in information. Limitations of the publication did not allow for an extensive review of the literature and a backup to recommendations. We will address the points raised by Dr Wittmer and colleagues below.

First, as stated, the Fibrosis-4 (FIB-4) Index for Liver Fibrosis test and an abdominal ultrasound are easy, non-invasive tests for evaluating SLD that are also relatively inexpensive. The FIB-4 test has been extensively evaluated in meta-analyses against liver biopsies and was found to be accurate at a FIB-4 cut-off score of 1.3 with a 98% to 99% negative predictive value.2,3 It is true the FIB-4 test is less accurate for detecting more advanced fibrosis,4 but others feel it is still useful in advanced fibrosis of stages F3 and higher.5 Studies on the best noninvasive way to predict advanced liver disease are ongoing. We stated that in patients 65 years and older the FIB-4 cut-off score is suggested to be higher. In patients with diabetes, the FIB-4 test is less predictive, partly because of a more rapid advancement of fibrosis.6 As such, measurement of liver stiffness is a more accurate way to determine advancing fibrosis in patients with diabetes.

Second, while the article does not mention therapeutic management, knowledge of estimation levels of fibrosis does suggest how to manage patients with MASLD. A 2015 study on paired liver biopsies followed fibrosis progression in patients with nonalcoholic fatty liver disease, which included, at baseline, one-third of patients without fibrosis, one-third with early fibrosis, and about one-third with more advanced fibrosis (≥F3, 6% cirrhosis).7 At an approximate 5-year follow-up, fibrosis progressed in one-third of patients, 40% stayed the same, and one-fifth improved.7

Third, a differential diagnosis of fatty liver disease is an important consideration. We agree that family practitioners do not need to rule out rare causes of steatosis but should be aware of them. The article states it is important to establish how much alcohol intake may contribute to SLD.

Fourth, we feel that once SLD has been diagnosed, the risk of a number of causes of mortality is unmasked and raises a red flag. A 2019 meta-analysis of 14 studies reported an increase in all-cause mortality (hazard ratio=1.34, 95% CI 1.17 to 1.54); this was independent of age, sex, or years of follow-up appointments, body mass index (BMI), and presence of diabetes.8 The study did not find an increased risk of cardiovascular disease (CVD) or cancer mortality. However, a different study found an increased risk of mortality from CVD, cancer, and liver disease in women.9 In another study, high levels of triglycerides were associated with all-cause mortality, CVD, and diabetes, especially in patients with a high BMI.10

Fifth, as stated in the article, follow-up at yearly intervals is an opinion based on the signal for accompanying and future disease risks. It is true the Alberta Health Services care pathway referenced in the article recommends a 2- to 3-year follow-up for liver disease.1 It is also true there are no precise studies that analyze cost benefits. However, several factors must be considered. While in younger, apparently healthy patients progression of 1 grade of fibrosis is about 14 years; this is faster with metabolic dysfunction–associated steatohepatitis (MASH) at 7 years.7 This is also true for patients with diabetes.6 There is also the risk of increased hepatocellular carcinoma, which is higher in more advanced fibrosis stages (0.5% to 2.6% of patients with MASH cirrhosis), but is still present in any fibrotic stages (0.01% to 0.13% of patients without cirrhosis).11

Finally, we disagree that diagnosing SLD will not alter patient outcomes. Patients at any level of fatty liver disease are unhealthy. Even when apparently young healthy patients are diagnosed, with time, there is risk of developing associated comorbidities. These patients could fall under the rubric of the chronic care model in which regular follow-ups impact patient outcomes.12 At any stage of fibrosis lifestyle changes should be repeatedly encouraged. Further, because MASLD is so frequent, there are many studies to find new treatments that will likely add to the therapeutic armamentarium.13

In the United States, resmetirom, a thyroid hormone receptor β agonist, is reserved for use in patients with stages F2 and F3 fibrosis. It has not yet been found to benefit patients with cirrhosis.14 Because patients with stages F2 and F3 fibrosis are diagnosed using vibration-controlled transient elastography or shear-wave elastography, treatment is currently relegated to hepatologists.15 Studies are ongoing in Canada. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists are also being studied for effects on MASLD and MASH.16 When there is an epidemic such as the one described here, efforts should be redoubled to follow patients with MASLD and consistently urge them to follow a healthier lifestyle.