Dear Editor,
We appreciate Drs. Ko and Mak’s interest in our paper [
1] with valuable comments [
2]. Hepatocellular carcinoma (HCC) surveillance is essential in identifying early-stage HCC, which curative therapy can be used with improving long-term outcomes [
3]. Nowadays, the uptake of HCC surveillance is under-practiced with poor adherence because of several reasons:
1. Some patients do not know they have chronic liver diseases.
2. No surveillance tools for HCC in at-risk patients other than hepatitis B virus or hepatitis C virus patients.
3. The inaccessibility to the HCC surveillance exams, such as abdominal ultrasonography or alpha-fetoprotein tests.
Recently, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been increasingly recognized because of the popularity of Western-style diets and sedentary lifestyles. MASLD is becoming a growing cause of HCC in addition to viral hepatitis. However, there is no recommendation for the surveillance strategy for MASLD patients because of the low risk of HCC and difficulty in performing abdominal ultrasound with the background of liver steatosis in obese individuals. The establishment of an HCC risk predictor in MASLD is thus an unmet clinical need. Accordingly, our study was focused on developing a risk predictor for patients with chronic liver diseases (CLDs, especially MASLD) other than viral hepatitis.
The steatosis-associated fibrosis estimator (SAFE) score contains commonly available parameters, including age, body mass index, presence of diabetes mellitus, aspartate aminotransferase, alanine aminotransferase, globulin and platelet count and has been used for liver fibrosis evaluation in patients with nonalcoholic fatty liver disease [
4]. Because the SAFE score correlated with liver fibrosis, we applied it to evaluate the risk of HCC in our study. We found the SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. A high SAFE score (≥100) increased the risks of HCC in subgroups of viral hepatitis and non-viral hepatitis, including MASLD (4-fold increased risks). This finding had been externally validated by another cohort from a tertiary medical center. We also validated our findings in a community cohort with the MASLD population, supporting the generalizability of the SAFE scores to predict the development of HCC regardless of etiologies of liver diseases in different clinical settings. To sum up, the SAFE score may be used as a universal HCC risk predictor to guide HCC surveillance.
In contrast to the HCC predictors using tumor markers, such as the GALAD score [
5], GAAD score [
6], or the ASAP score [
7], the SAFE score uses general clinical markers which is easier to use in our daily practice. We agree with Drs. Ko and Mak, who suggested the SAFE score can be built into the clinical computer system with readily available clinical parameters at a minimal additional cost. In patients of CLD with SAFE scores less than 100, they have a very low risk of HCC and can lengthen their interval for abdominal ultrasound exams or opt out of HCC surveillance. Because the SAFE score includes several modifiable parameters, the next step is to evaluate whether the dynamical increment of SAFE scores further increases the risk of HCC, just like the predictive role of serial elevation of alpha-fetoprotein levels in HCC prediction [
8]. Agreeingly, a future prospective study is required to assess the performance of the SAFE score in both primary care and hospital settings to identify at-risk populations for HCC surveillance.
FOOTNOTES
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Authors’ contribution
Tung-Hung Su: Conceptualization, Writing – original draft. Jia-Horng Kao: Writing – review & editing.
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Conflicts of Interest
T.-H. S. received research grant from Gilead Sciences, and was on speaker’s bureaus for Abbvie, Bayer, Bristol- Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, and Takeda. J.-H. K. has served as a consultant for Abbvie, Gilead Sciences, Merck Sharp and Dohme, and Roche and on speaker’s bureaus for Abbvie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp and Dohme.
Abbreviations
metabolic dysfunction-associated steatotic liver disease
Steatosis‐Associated Fibrosis Estimator
REFERENCES
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- 7. Lu YC, Su TH, Tseng TC, Hsu SJ, Liao SH, Hong CM, et al. High PIVKA-II level and ASAP score predict 1-year risk of hepatocellular carcinoma in non-cirrhotic chronic hepatitis B patients. Am J Cancer Res 2023;13:2588-2597.
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