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

Angela Puente,Jose Ignacio Fortea,Laura Rasines,Miguel Posadas,Agustin Garcia Blanco,Paula Iruzubieta,Joaquin Cabezas,Javier Crespo,Emilio Fábrega,Susana Llerena,Maria Teresa Arias Loste

doi:10.3390/jcm8081242

Abstract

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 n = 59 (21.7%); F3 n = 44 (16.05%); and 100 were F4 (36.9%). Although the LSM (absolute value) improved in 82% of patients (n = 222), it progressed in 17.5% of patients (n = 48). At 24 M, 48 patients met the metabolic syndrome (MetS) criteria and there was an increase in patients with a BMI of >25 kg/m2 (p < 0.001). At B and 24 M, a BMI of >25 kg/m2 is a risk factor for significant fibrosis or steatosis at 24 M (p < 0.05) and progression on LSM (p < 0.001), as well as MetS at B and 24 M (OR 4.1 IC (1.4–11.7), p = 0.008; and OR 5.4 IC (1.9–15.4), p = 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 (p < 0.001) with higher serological value in patients with elastography of >9 kPa vs. <9 kPa (p = 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.

Highlights

Patients with chronic hepatitis C virus have experienced radical changes in the evolution of their disease after the appearance of new direct-acting antivirals, achieving virological healing rates of over 95%, even in very advanced phases of the disease [1]
Previous studies have shown that up to 15% of patients with chronic HCV liver disease do not achieve fibrosis regression, and this fact can occur both in the advanced and earlier stages [6]. This suggests that regression depends on the so-called point of no return, but there may be cofactors that can be key in this progression and they are often not sufficiently evaluated in this patient group [2,7,8]
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Summary

Introduction

Patients with chronic hepatitis C virus have experienced radical changes in the evolution of their disease after the appearance of new direct-acting antivirals, achieving virological healing rates of over 95%, even in very advanced phases of the disease [1]. Previous studies have shown that up to 15% of patients with chronic HCV liver disease do not achieve fibrosis regression (as determined by elastographic methods), and this fact can occur both in the advanced and earlier stages [6]. This suggests that regression depends on the so-called point of no return (thickened fibrotic septa and clinically significant portal hypertension), but there may be cofactors (such as metabolic syndrome or alcohol) that can be key in this progression and they are often not sufficiently evaluated in this patient group [2,7,8]. Stellate and Kupffer cells (liver macrophages) are the key element in fibrogenesis, and the activation of Ly6Chigh macrophages is the basis for regression [12,13,14]

Objectives

Methods

Conclusion