Letter to the Editor Regarding “Liver Stiffness Measurements After Oral Antivirals Effectively Predict the Risk of HCC in Patients With Chronic Hepatitis C”

We read with great interest the recent article by Lee et al. titled “Liver Stiffness Measurements After Oral Antivirals Effectively Predict the Risk of HCC in Patients With Chronic Hepatitis C” [1]. As a clinical hepatologist with over a decade of experience managing patients with CHC and HCC, we appreciate the authors' efforts to address a critical unmet need: identifying HCC risk after SVR to DAAs. The focus on longitudinal LSM as a dynamic predictor is particularly valuable, as it moves beyond static baseline assessments that often fail to capture post-treatment changes in liver health. However, several points need further discussion and refine future research. First, the absence of liver biopsy data weakens the link between LSM improvements and actual fibrosis regression—a key assumption of the study. The authors report that LSM decreased from 11.5 kPa at baseline to 8.3 kPa at 1 year post-SVR, but LSM is a surrogate marker that reflects both fibrosis and inflammation [2]. In clinical practice, we often see patients with post-DAA LSM reductions driven primarily by resolution of necroinflammation, not true fibrosis reversal. Without histological confirmation, it is unclear whether the “low-risk” LSM group (LSM < 10 kPa) actually has less underlying fibrosis—or simply less inflammation—than their baseline status. This distinction matters: A patient with persistent advanced fibrosis but reduced inflammation may still face substantial HCC risk, even with a “normalized” LSM. Second, the exclusion of patients who developed HCC or died within 1 year of SVR creates a critical gap in assessing short-term risk. The authors note this limitation but do not discuss its clinical impact: In real-world practice, a small but meaningful subset of CHC patients (particularly those with baseline cirrhosis) develop HCC within 12 months of SVR [3, 4]. These patients would have been excluded from the study, yet they represent a group that requires immediate, not delayed, surveillance. By focusing solely on risk after 1 year, the study overlooks the need for early monitoring in high-risk patients and may lead clinicians to underestimate short-term HCC risk in post-SVR cohorts. Third, this study includes 16.8% of patients with fatty liver and 34.6% with obesity, yet it neither addresses how these conditions impact the reliability of LSM measurements nor adjusts for this issue in its risk models. The LSM method used in this study is transient elastography, and ample evidence has documented that this method overestimates liver stiffness in patients with severe steatosis—severe steatosis leads to increased ultrasound attenuation that skews the results. In contrast, it underestimates liver stiffness in obese patients, as obesity impairs the probe's ability to penetrate to the liver, resulting in inaccurate readings. Finally, the underrepresentation of metabolic comorbidities—such as nonalcoholic fatty liver disease (NAFLD) and poorly controlled diabetes—limits the study's relevance to modern CHC care. The authors mention that diabetes was more common in HCC patients but do not report data on diabetes duration, glycemic control, or NAFLD prevalence. Today, many CHC patients have concurrent NAFLD (often termed “double hit” liver disease), which independently increases HCC risk even after HCV eradication. By not accounting for these comorbidities, the study's LSM-based risk model may underestimate risk in patients with overlapping metabolic liver disease—a growing segment of the post-DAA population. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.