Letter to the Editor: Does therapeutic plasma exchange really have a role in the treatment of hepatocellular carcinoma?

Abstract

To the editor, We read with great interest the article by Oh et al. [1] Below are our criticisms and comments about the study:1. The knowledge about immune checkpoint molecules and immune checkpoint inhibitors in the abstract and introduction sections of the article should be corrected. Namely, Programmed Cell Death Ligand 1 (PD-L1) is an immune checkpoint molecule, not an immune checkpoint inhibitor. Also, the main target of therapeutic plasma exchange (TPE) should be to eliminate immune checkpoint molecules such as Programmed cell death protein 1 and PD-L1, not immune checkpoint inhibitors. 2. The researchers detected the 5-year cumulative incidence of HCC-specific recurrence-free survival to be higher in the post-transplant (TPE) (+) group compared to the post-transplant TPE (−) group. [1] However, they could not reveal relevant differences in median overall survival between the 2 groups [80.3% (95% Cl: 69.1%-93.2%) vs. 72.1% (95 Cl: 60.0%-86.6%), p = 0.318]. [1] Although surrogate radiology-based end points for OS, median overall survival is the gold standard end point in demonstrating the clinical benefit of systemic, locoregional, and surgical treatments in HCC. [2] 3. Given that HCC is a very heterogenous tumor, studying only microvascular invasion as a prognostic marker in HCC, but not investigating HCC differentiation, microscopic satellites, and histological variants, are relevant limitations of this study. 4. The investigators do not explain why TPE is more effective in patients with poor prognostic factors, such as microvascular invasion and being outside of Milan criteria. 5. HCC cells constitute a tumor microenvironment that promotes their growth and immune evasion. [3] Immune checkpoint molecules and ligands (eg, Programmed cell death protein 1, PD-L1) are among the key elements of the tumor microenvironment. The tumor microenvironment plays a critical role in both the response to molecular-targeted therapies and immune evasion. [3] PD-L1 is overexpressed in some cancers, such as melanoma and breast cancer, but its expression is quite low in HCC. Therefore, we cannot agree with the view that TPE improves recurrencefree survival rates by performing PD-L1 clearance in this study. Furthermore, according to the ASFA guidelines, TPE is not recommended in HCC. [4] CONFLICTS OF INTERESTThe authors have no conflicts to report.