Changes in Circulating Lysyl Oxidase-Like-2 (LOXL2) Levels, HOMA, and Fibrosis after Sustained Virological Response by Direct Antiviral Therapy

• Main Authors: Angela Puente, Jose Ignacio Fortea, Miguel Posadas, Agustin Garcia Blanco, Laura Rasines, Joaquin Cabezas, Maria Teresa Arias Loste, Susana Llerena, Paula Iruzubieta, Emilio Fábrega, Javier Crespo
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: Journal of Clinical Medicine
• Subjects: SVR; liver fibrosis; LOXL2; portal hypertension; fibrosis regression
• Online Access: https://www.mdpi.com/2077-0383/8/8/1242

Background: we aimed to assess the influence of metabolic syndrome on fibrosis regression (using liver-stiffness measurement (LSM) and serological scores) and the relationship with the expression of lysyl oxidase-like-2 as a potential goal of antifibrotic therapy. Methods: We included 271 patients treated with Direct Antiviral Therapy (DAAs) in our hospital who achieved a sustained virological response (SVR); physical examination, blood tests, and LSM were made at baseline (B) and 24 months (24 M) after SVR. Hemodynamic studies and transjugular liver biopsies were performed on 13 patients. Results: At B, 68 patients were F1 (25.1%); F2 <i>n</i> = 59 (21.7%); F3 <i>n</i> = 44 (16.05%); and 100 were F4 (36.9%). Although the LSM (absolute value) improved in 82% of patients (<i>n</i> = 222), it progressed in 17.5% of patients (<i>n</i> = 48). At 24 M, 48 patients met the metabolic syndrome (MetS) criteria and there was an increase in patients with a BMI of &gt;25 kg/m² (<i>p</i> &lt; 0.001). At B and 24 M, a BMI of &gt;25 kg/m² is a risk factor for significant fibrosis or steatosis at 24 M (<i>p</i> &lt; 0.05) and progression on LSM (<i>p</i> &lt; 0.001), as well as MetS at B and 24 M (OR 4.1 IC (1.4&#8722;11.7), <i>p</i> = 0.008; and OR 5.4 IC (1.9&#8722;15.4), <i>p</i> = 0.001, respectively). Regarding the correlation between LSM and the liver biopsy, we found that only six out of 13 patients had a matching LSM and biopsy. We found a statistically significant decrease in LOXL2 levels at 24 M with respect to B (<i>p</i> &lt; 0.001) with higher serological value in patients with elastography of &gt;9 kPa vs. &lt;9 kPa (<i>p</i> = 0.046). Conclusion: Regression of LSM was reached in 82% of patients. Downregulated LOXL2 was demonstrated post-SVR, with overexpression in cirrhotic patients being a potential therapy goal in selected patients.