Prospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2018; 24(11): 1269-1277
Published online Mar 21, 2018. doi: 10.3748/wjg.v24.i11.1269
Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals
Mazen Noureddin, Micaela M Wong, Tsuyoshi Todo, Shelly C Lu, Arun J Sanyal, Edward A Mena
Mazen Noureddin, Fatty Liver Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Mazen Noureddin, Shelly C Lu, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Micaela M Wong, Edward A Mena, California Liver Research Institute, Pasadena, CA 91105, United States
Tsuyoshi Todo, Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Arun J Sanyal, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States
Author contributions: Noureddin M provided the study concept and design; Noureddin M, Wong MM and Mena EA contributed to acquisition of data; Noureddin M, Wong MM, Todo T, Lu SC and Sanyal AJ contributed to analysis and interpretation of data; Noureddin M drafted the manuscript; Noureddin M, Wong MM, Todo T, Lu SC, Sanyal AJ and Mena EA contributed to critical revision of the manuscript for important intellectual content; Noureddin M contributed to the statistical analysis; Noureddin M and Mena EA provided administrative and technical support and study supervision; Wong MM provided support for carrying out the study; all authors gave final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Institutional review board statement: This study was approved by the Central Institutional Review Board.
Informed consent statement: Informed voluntary consent was acquired from all the study participants.
Conflict-of-interest statement: Noureddin M has been on the advisory board or a speaker for EchoSens North America, OWL, Intercept and Abbott; Noureddin M has received research support from Gilead, Galmed, Galectin, Conatus, Zydus and Shire; Noureddin M is a minor shareholder of Anaetos; Sanyal AJ has been a consultant to Intercept, Galectin, BMS, Nitto Denko, Nimbus, Aredlyx, Vivelyx, and Tandeva; Sanyal AJ has received grants from Gilead, Intercept, Novartis, Merck, BMS, and Tobira; Sanyal AJ has stock or stock options in Genfit, Akarna, Tiziana, Natural Shield, Durect, and Exhalenz. Mena EA has received research support from Galmed, Conatus, Shire, Merck and Gilead; Mena EA has been a consultant and advisor to Gilead, Abbvie, Merck, Bayer, and Grifalos; Mena EA is a member of the speakers’ bureaus for Gilead, Abbvie, Merck, Bayer, Echosens North America and Grifalos; Mena EA owns stocks in Gilead and Galectin; The other authors report no conflicts of interest.
Data sharing statement: The statistical code and dataset are available from the corresponding author at Consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Mazen Noureddin, MD, MHSc, Associate Professor, Division of Digestive and Liver Diseases, Comprehensive Transplant Program, Cedars-Sinai Medical Center, 8900 Beverly Blvd, Suite 250, Los Angeles, CA 90048 United States.
Telephone: +1-310-4237088 Fax: +1-310-2488197
Received: December 3, 2017
Peer-review started: December 5, 2017
First decision: December 14, 2017
Revised: January 27, 2018
Accepted: March 3, 2018
Article in press: March 3, 2018
Published online: March 21, 2018

To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.


Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded.


One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) (P < 0.05). Post-SVR, 48 patients (47.5%) had steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P < 0.05. Interestingly, compared to baseline, both patients with and without steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, (P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness (≥ 7 kPa).


Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.

Keywords: Nonalcoholic fatty liver disease, Hepatitis C, Fibrosis, Steatosis, Sustained virological response, Direct-acting antivirals

Core tip: This is the first prospective study to assess the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals. The study’s findings that fatty liver is present in 47.5% of these patients and that some steatotic patients have clinically significant fibrosis despite normal liver enzymes should raise awareness of the post-sustained virological response (SVR) prevalence of fatty liver and the importance of post-SVR assessment of steatosis and fibrosis and long-term follow up with these patients.