Scientific Reports (May 2024)

Lysyl oxidase-like 2 as a predictor of hepatocellular carcinoma in patients with hepatitis C virus after sustained virological response

  • Takeshi Chida,
  • Kazuyoshi Ohta,
  • Hidenao Noritake,
  • Masahiro Matsushita,
  • Gou Murohisa,
  • Fujito Kageyama,
  • Yuzo Sasada,
  • Tatsuki Oyaizu,
  • Minoru Tsugiki,
  • Katsutoshi Tamakoshi,
  • Takeyuki Nakajima,
  • Takafumi Suda,
  • Kazuhito Kawata

DOI
https://doi.org/10.1038/s41598-024-61366-y
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 12

Abstract

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Abstract Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.

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