Evaluation of advanced fibrosis measured by transient elastography after hepatitis C virus protease inhibitor-based triple therapy Federico Sáez-Royuela a , Pedro Linares c , Luis A. Cervera a , Carolina Almohalla d , Francisco Jorquera c , Sara Lorenzo e , Isidro García f , Guillermo Karpman g , Ester Badia a , María A. Vallecillo d , Adriana Moncada a , Sara Calvo b and José L. Olcoz c ; Asociación Castellano y Leonesa de Hepatología (ACyLHE) Aim Few studies have investigated the course of liver stiffness after treatment with protease inhibitors. We evaluated the impact of this therapy on liver fibrosis measured by transient elastography. Methods This multicenter observational, cohort, prospective study included 90 patients with hepatitis C genotype 1 treated with telaprevir or boceprevir who had advanced fibrosis evidenced by liver stiffness (≥9.5 kPa). Liver stiffness was measured at baseline and 24 weeks after treatment ended, and was compared with virological responses at week 12. Results Liver stiffness decreased in 89% of patients who achieved sustained virological response. The median intrapatient liver stiffness value at the end of follow-up decreased by 5.1 kPa (35%) from baseline compared with 0.1 kPa (0.5%) in those who did not achieve a sustained virological response (P < 0.001). The liver stiffness level fell below 9.5 kPa in 58% of patients with sustained virological response, and 71% of those with sustained virological response and cirrhosis evidenced by liver stiffness at baseline achieved regression below 12.5 kPa by the end of follow-up. Sustained virological response was the only variable associated with improved liver stiffness in multivariate analysis (odds ratio: 17.3; 95% confidence interval: 4.4–67.6; P < 0.001). Conclusion In patients with advanced fibrosis measured by transient elastography at the beginning of protease inhibitor-based therapy with sustained virological response, liver stiffness was significantly reduced 24 weeks after treatment. This suggests the possibility of liver cirrhosis evidenced by liver stiffness regression after sustained virological response in a significant proportion of patients. Eur J Gastroenterol Hepatol 28:305–312 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Introduction Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. Its long-term impact ranges from minimal changes to extensive fibrosis and cirrhosis with or without hepatocellular carcinoma (HCC) [1]. The objective of chronic hepatitis C (CHC) treatment is to achieve sustained virological response (SVR) – the absence of viral replication at 12 or 24 weeks after treat- ment completion. SVR is stable over time, reduces mor- bidity and mortality, and is equivalent in most cases to curing the HCV infection [2,3]. However, complications such as HCC can appear, even years later, in patients with SVR who have residual fibrosis [4–6]. Assessment of residual liver fibrosis in patients who achieve SVR is strategically important for prognostication and for defin- ing cost-effective surveillance programs for liver-related complications [7]. The hepatic fibrosis stage is the principal predictor of liver disease progression that drives treatment indications [8]. Historically, a liver biopsy has been the gold standard for staging liver fibrosis [8]. However, because it is an invasive and expensive technique with sampling errors and intraobserver and interobserver variability, noninvasive methods such as the FibroTest or transient elastography (TE), which measures liver stiffness (LS), are currently preferred in patients with CHC [9–12]. LS measured by TE correlates well with liver fibrosis and excellently with cir- rhosis determined by liver biopsy [13,14]. Therefore, TE is considered a surrogate marker of fibrosis [15,16]. TE has been validated for diagnosing liver-related complications and has a high prognostic value for predicting liver-related death and overall survival [6,12,13,17,18]. Studies have assessed the evolution of liver fibrosis after antiviral treatment of hepatitis C with pegylated interferon (Peg-IFN) and ribavirin (RBV) through liver biopsies. These studies have demonstrated that antiviral therapy can improve liver histology [4,7,19–21], although few cirrhosis patients have been evaluated [22]. Subsequently, non- invasive methods, and especially TE, have been used to estimate the impact of treatment and SVR in the progres- sion of fibrosis in patients treated with Peg-IFN and RBV [6,16,23–29]. The development of direct antiviral agents (DAAs) such as HCV protease inhibitors (PIs), boceprevir a Department of Gastroenterology and Hepatology, b Burgos Foundation for Health Research, Hospital Universitario de Burgos, Burgos, c Department of Gastroenterology and Hepatology, Complejo Asistencial Universitario León, León, d Department of Hepatology, Hospital Universitario Rio Hortega, e Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Valladolid, Valladolid, f Department of Gastroenterology and Hepatology, Complejo Asistencial Palencia, Palencia and g Department of Gastroenterology and Hepatology, Hospital El Bierzo, Ponferrada, Spain Correspondence to Federico Sáez-Royuela, PhD, MD, Department of Gastroenterology and Hepatology, Hospital Universitario de Burgos, Avda, Islas Baleares 3, 09006 Burgos, Spain Tel: + 34 608 908 550; fax: + 34 947 281 829; e-mail: fsroyuela@gmail.com Received 13 August 2015 Accepted 21 October 2015 European Journal of Gastroenterology & Hepatology 2016, 28:305–312 Keywords: chronic, elasticity imaging techniques, fibrosis, hepatitis C, liver cirrhosis, therapy ’ Original article 0954-691X Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MEG.0000000000000533 305 Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.